gebhart/patrepeval huggingface dataset:
HOXC10 Expression Supports the Development of Chemotherapy Resistance by Fine Tuning DNA Repair in Breast Cancer Cells (2016)

Development of drug resistance is a major factor limiting the continued success of cancer chemotherapy. To overcome drug resistance, understanding the underlying mechanism(s) is essential. We found that HOXC10 is overexpressed in primary carcinomas of the breast, and even more significantly in distant metastasis arising after failed chemotherapy. High HOXC10 expression correlates with shorter recurrence-free and overall survival in patients with estrogen receptor-negative breast cancer undergoing chemotherapy. We found that HOXC10 promotes survival in cells treated with doxorubicin, paclitaxel, or carboplatin by suppressing apoptosis and upregulating NF-κB Overexpressed HOXC10 increases S-phase-specific DNA damage repair by homologous recombination (HR) and checkpoint recovery in cells at three important phases. For double-strand break repair, HOXC10 recruits HR proteins at sites of DNA damage. It enhances resection and lastly, it resolves stalled replication forks, leading to initiation of DNA replication following DNA damage. We show that HOXC10 facilitates, but is not directly involved in DNA damage repair mediated by HR. HOXC10 achieves integration of these functions by binding to, and activating cyclin-dependent kinase, CDK7, which regulates transcription by phosphorylating the carboxy-terminal domain of RNA polymerase II. Consistent with these findings, inhibitors of CDK7 reverse HOXC10-mediated drug resistance in cultured cells. Blocking HOXC10 function, therefore, presents a promising new strategy to overcome chemotherapy resistance in breast cancer. Cancer Res; 76(15); 4443-56. ©2016 AACR.
Interaction between ApoB and Hepatic Lipase Mediates the Uptake of ApoB-containing Lipoproteins (1998)

Hepatic lipase (HL) on the surface of hepatocytes and endothelial cells lining hepatic sinusoids, the adrenal glands, and the ovary hydrolyzes triglycerides and phospholipids of circulating lipoproteins. Its expression significantly enhances low density lipoprotein (LDL) uptake via the LDL receptor pathway. A specific interaction between LPL, a homologous molecule to HL, and apoB has been described (Choi, S. Y., Sivaram, P., Walker, D. E., Curtiss, L. K., Gretch, D. G., Sturley, S. L., Attie, A. D., Deckelbaum, R. J., and Goldberg, I. J. (1995) J. Biol. Chem. 270, 8081-8086). The present studies tested the hypothesis that HL enhances the uptake of lipoproteins by a specific interaction of HL with apoB. On a ligand blot, HL bound to apoB26, 48, and 100 but not to apoE or apoAI. HL binding to LDL in a plate assay with LDL-coated plates was significantly greater than to bovine serum albumin-coated plates. Neither heat denatured HL nor bacterial fusion protein of HL bound to LDL in the plate assays. 125I-LDL bound to HL-saturated heparin-agarose gel with a Kd of 52 nM, and somewhat surprisingly, this binding was not inhibited by excess LPL. In cell culture experiments HL enhanced the uptake of 125I-LDL at both 4 and 37 degreesC. The enhanced binding and uptake of LDL was significantly inhibited by monoclonal anti-apoB antibodies. In contrast to LPL, both amino- and carboxyl-terminal antibodies blocked the apoB interaction with HL to the same extent. Thus, we conclude that there is a unique interaction between HL and apoB that facilitates the uptake of apoB-containing lipoproteins by cells where HL is present.
Genuine memory deficits in dementia (1987)

Controlled learning with effective cued recall is needed to distinguish between genuine memory deficits due to impairment of specific memory processes and apparent memory deficits due to impairment of other cognitive processes, such as attention, that can limit memory. Effective cued recall is needed for accurate measurement of memory in the elderly because cued recall reveals learning not shown by free recall. When a search procedure was used to control processing for effective encoding and cued recall, nondemented elderly adults recalled all or nearly all 16 items on each trial. Decreased recall by demented patients even after they carried out the same effective processing showed genuine memory impairment that was not due to other cognitive deficits. Cued recall was better than either free recall or recognition in discriminating elderly persons with dementia from those without dementia and by itself accounted for 75 % of the variation in dementia status. Cued recall was especially useful for identifying patients with mild to moderate dementia who were not identified by free recall. It is proposed that elderly persons who have decreased cued recall of a 16‐item list after controlled learning have genuine memory impairment and therefore are likely to be demented because other causes of amnestic syndromes are relatively infrequent in the aged. Controlled learning with effective cued recall should be useful for screening of elderly persons for dementia.
Prenatal Determination of Fetal Rhesus D Status by DNA Amplification of Peripheral Blood of Rhesus‐Negative Mothers (1994)

We have developed a sensitive PCR-based assay for the RhD gene and used it to detect circulating fetal cells from RhD-positive fetuses from peripheral blood of RhD-negative mothers. With further improvement in diagnostic accuracy, this assay may have implications in the management of RhD-sensitized pregnancies in women whose partners are heterozygous for the RhD gene. Further studies are required to determine the relationship between maternal anti-D levels and circulating fetal cell numbers.
A new model of diffuse brain injury in rats (1994)

This report describes the development of an experimental head injury model capable of producing diffuse brain injury in the rodent. A total of 161 anesthetized adult rats were injured utilizing a simple weight-drop device consisting of a segmented brass weight free-falling through a Plexiglas guide tube. Skull fracture was prevented by cementing a small stainless-steel disc on the calvaria. Two groups of rats were tested: Group 1, consisting of 54 rats, to establish fracture threshold; and Group 2, consisting of 107 animals, to determine the primary cause of death at severe injury levels. Data from Group 1 animals showed that a 450-gm weight falling from a 2-m height (0.9 kg-m) resulted in a mortality rate of 44% with a low incidence (12.5%) of skull fracture. Impact was followed by apnea, convulsions, and moderate hypertension. The surviving rats developed decortication flexion deformity of the forelimbs, with behavioral depression and loss of muscle tone. Data from Group 2 animals suggested that the cause of death was due to central respiratory depression; the mortality rate decreased markedly in animals mechanically ventilated during the impact. Analysis of mathematical models showed that this mass-height combination resulted in a brain acceleration of 900 G and a brain compression gradient of 0.28 mm. It is concluded that this simple model is capable of producing a graded brain injury in the rodent without a massive hypertensive surge or excessive brain-stem damage.
Nearest neighbor queries in metric spaces (1997)

Given a set Sofn sites (points), andadistance measure cl, the nearest neighbor searching problem, or post office problem, istobuild adatastructure sothatgiven a query point q, the site nearest to g can be found quickly. This paper gives data structures for this problem when the sites and queries are in a metric space. The data structures can be analyzed when the metric space satisfies a certain spherepacking bound. Onedata structure, denoted D(S), requires expected O(n)(lgn)O(lK 1gT(s)) time to build. Here 'Y(S) is the distance ratio of S, the ratio of the distance between the farthest pair of points in S to the distance between the closest pair. The constant factors in the bound depend on the sphere-packing bound. When the query pointqis arandom element of {q} uS, as for example when q and the points of S are randomly generated from a common distribution, then the query time is expected (lgn)O(lglgrfs)).
Review: Genetic and Epigenetic Aspects of Cloning and Potential Effects on Offspring of Cloned Mammals (2004)

Although the biological mechanisms by which host cytoplasm and donor nuclei interact to produce a developmentally competent reconstructed embryo remain largely unknown, some advances have been made to our understanding of the genetic and epigenetic factors involved in the of reprogramming of the donor nucleus. Genetic alterations, which comprise changes to the genetic information in both the nuclear and cytoplasm compartments, are passed on to subsequent generations at fertilization and are a potential source of variation among cloned animals and their offspring. Apart from the major chromosomal anomalies found in developmentally arrested embryos and fetuses, less detrimental rearrangements and/or mutations are likely to go unnoticed in most donor cell karyotypes, suggesting that such problems could lead to inheritable anomalies among clones and their offspring. Mitochondrial DNA is also relevant to cloning because most animals inherit most or all of their mitochondria from the host oocyte. Epigenetic alterations to the DNA or to the histone packaging proteins are independent of gene sequences. Aberrant epigenetic events may lead to variable gene expression or mitosis and consequent effects on development and phenotype. Although much of the epigenetic marking is reset during embryogenesis and development, the impact of epimutations on progeny remains unexplored.
Agalsidase therapy in patients with Fabry disease on renal replacement therapy: a nationwide study in Italy (2007)

Kidney transplantation should be the standard of care for Fabry patients progressing towards ESRD. Transplanted Fabry patients on ERT may do better than patients remaining on maintenance dialysis. Larger, controlled studies in Fabry patients with ESRD will have to demonstrate if ERT is able to change the trajectory of cardiac disease and can preserve graft renal function.
Genomics: the implications for ethics and education (1999)

Over the past 10 years, the identification of disease genes has been expanding rapidly. Those identified in the earlier part of the decade were largely achieved through positional cloning and the majority are for relatively rare disorders which involve single genes. As the Human Genome Mapping Project has progressed, the rate of gene discovery has increased substantially through the development of new DNA sequencing techniques and in silico approaches. The human genome will have been largely sequenced by ther Spring 2000. We can expect the identification of large numbers of susceptibility genes for common multifactorial polygenic diseases as well as genes which are associated with human behavioural traits. Some of these advances hold out the prospects of real progress in the diagnosis and treatment of a wide range of disorders. However, for many individuals, increased knowledge about their genes will present ethical dilemmas which are difficult to resolve. There are also wider ethical issues which concern the use of genetic information by insurers and employers and yet others which concern ownership and access. In this chapter, the main ethical issues raised by the impact of genomics on healthcare are discussed. The role of education in enabling individuals and health professionals to meet these challenges is also considered.
Stabilizers as a design tool for new forms of the Lechner-Hauke-Zoller annealer (2016)

In a recent paper, Lechner, Hauke, and Zoller (LHZ) described a means to translate a Hamiltonian of <i>N</i> spin-<sup>1</sup>/<sub>2</sub> particles with "all-to-all" interactions into a larger physical lattice with only on-site energies and local parity constraints. LHZ used this mapping to propose a novel form of quantum annealing. We provide a stabilizer-based formulation within which we can describe both this prior approach and a wide variety of variants. Examples include a triangular array supporting all-to-all connectivity as well as arrangements requiring only 2<i>N</i> or <i>N</i> log <i>N</i> spins but providing interesting bespoke connectivities. Further examples show that arbitrarily high-order logical terms can be efficiently realized, even in a strictly two-dimensional layout. Our stabilizers can correspond to either even-parity constraints, as in the LHZ proposal, or odd-parity constraints. Considering the latter option applied to the original LHZ layout, we note that it may simplify the physical realization because the required ancillas are only spin-<sup>1</sup>/<sub>2</sub> systems (that is, qubits rather than qutrits); moreover, the interactions are very simple. We make a preliminary assessment of the impact of these design choices by simulating small (few-qubit) systems; we find some indications that the new variant may maintain a larger minimum energy gap during the annealing process.
Working with persistent objects: to swizzle or not to swizzle (1992)

Pointer swizzling is the conversion of database objects between an external form (object identifiers) and an internal form (direct memory pointers). Swizzling is used in some object-oriented databases, persistent object stores, and persistent and database programming language implementations to speed manipulation of memory resident data. The author describes a simplifying model of application behavior, revealing those aspects where swizzling is most relevant in both benefits and costs. The model has a number of parameters, which the authors have measured for a particular instance of the Mneme persistent object store, varying the swizzling technique used. The results confirm most of the intuitive, qualitative tradeoffs, with the quantitative data showing that some performance differences between schemes are smaller than might be expected. However, there are some interesting effects that run counter to naive intuition, most of which are explained using deeper analysis of the algorithms and data structures.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Adaptive OFDM for wideband radio channels (2002)

An OFDM (orthogonal frequency division multiplexing) transmission system is simulated with time-variant transfer functions measured with a wideband channel sounder. The individual subcarriers are modulated with fixed and adaptive signal alphabets. Furthermore, a frequency-independent as well as the optimum power distribution are used. The simulations show that with adaptive OFDM, the required signal power for an error probability of 10/sup -3/ can be reduced by 5...15 dB compared with fixed OFDM. The fraction of channel capacity which can be achieved with adaptive OFDM depends on the average signal-to-noise ratio and the propagation scenario.
Nanobodies® Specific for Respiratory Syncytial Virus Fusion Protein Protect Against Infection by Inhibition of Fusion (2011)

Despite the medical importance of respiratory syncytial virus (RSV) infections, there is no vaccine or therapeutic agent available. Prophylactic administration of palivizumab, a humanized monoclonal RSV fusion (F) protein-specific antibody, can protect high-risk children. Previously, we have demonstrated that RSV can be neutralized by picomolar concentrations of a camelid immunoglobulin single-variable domain that binds the RSV protein F (F-VHHb nanobodies). Here, we investigated the mechanism by which these nanobodies neutralize RSV and tested their antiviral activity in vivo. We demonstrate that bivalent RSV F-specific nanobodies neutralize RSV infection by inhibiting fusion without affecting viral attachment. The ability of RSV F-specific nanobodies to protect against RSV infection was investigated in vivo. Intranasal administration of bivalent RSV F-specific nanobodies protected BALB/c mice from RSV infection, and associated pulmonary inflammation. Moreover, therapeutic treatment with these nanobodies after RSV infection could reduce viral replication and reduced pulmonary inflammation. Thus, nanobodies are promising therapeutic molecules for treatment of RSV.
Independent component analysis for EEG source localization (2000)

We consider a spatiotemporal method for source localization, taking advantage of the entire EEG time series to reduce the configuration space we must evaluate. The EEG data are first decomposed into signal and noise subspaces using a principal component analysis (PCA) decomposition. This partitioning allows us to easily discard the noise subspace, which has two primary benefits: the remaining signal is less noisy, and it has lower dimensionality. After PCA, we apply independent component analysis (ICA) on the signal subspace. The ICA algorithm separates multichannel data into activation maps due to temporally independent stationary sources. For each activation map we perform an EEG source localization procedure, looking only for a single dipole per map. By localizing multiple dipoles independently, we substantially reduce our search complexity and increase the likelihood of efficiently converging on the correct solution.
Noninvasive detection of changes in membrane potential in cultured neurons by light scattering. (1991)

We report a procedure to detect electrical activity in cultured neurons by changes in their intrinsic optical properties. Using dark-field microscopy to detect scattered light, we observe an optical signal that is linearly proportional to the change in the membrane potential. Action potentials can be recorded without signal averaging. We use the dark-field method to show that there are substantial time delays between activity in the soma and in fine distal processes of identified Aplysia neurons. The biophysical basis for the change in optical properties of the neuron was deduced from measurements of the angular distribution of scattered laser light. An analysis of the data indicates that the radial component of the index of refraction of the membrane increases and the tangential components decrease concomitant with an increase in membrane potential. This is suggestive of a rapid reorientation of dipoles in the membrane during an action potential.
A Texture-based Method for Detecting Moving Objects (2004)

The detection of moving objects from video frames plays an important and often very critical role in different kinds of machine vision applications including human detection and tracking, traffic monitoring, humanmachine interfaces and military applications, since it usually is one of the first phases in a system architecture. A common way to detect moving objects is background subtraction. In background subtraction, moving objects are detected by comparing each video frame against an existing model of the scene background. In this paper, we propose a novel block-based algorithm for background subtraction. The algorithm is based on the Local Binary Pattern (LBP) texture measure. Each image block is modelled as a group of weighted adaptive LBP histograms. The algorithm operates in real-time under the assumption of a stationary camera with fixed focal length. It can adapt to inherent changes in scene background and can also handle multimodal backgrounds.
Discovery of a selective Na V 1.7 inhibitor from centipede venom with analgesic efficacy exceeding morphine in rodent pain models (2013)

Loss-of-function mutations in the human voltage-gated sodium channel NaV1.7 result in a congenital indifference to pain. Selective inhibitors of NaV1.7 are therefore likely to be powerful analgesics for treating a broad range of pain conditions. Herein we describe the identification of µ-SLPTX-Ssm6a, a unique 46-residue peptide from centipede venom that potently inhibits NaV1.7 with an IC50 of ∼25 nM. µ-SLPTX-Ssm6a has more than 150-fold selectivity for NaV1.7 over all other human NaV subtypes, with the exception of NaV1.2, for which the selectivity is 32-fold. µ-SLPTX-Ssm6a contains three disulfide bonds with a unique connectivity pattern, and it has no significant sequence homology with any previously characterized peptide or protein. µ-SLPTX-Ssm6a proved to be a more potent analgesic than morphine in a rodent model of chemical-induced pain, and it was equipotent with morphine in rodent models of thermal and acid-induced pain. This study establishes µ-SPTX-Ssm6a as a promising lead molecule for the development of novel analgesics targeting NaV1.7, which might be suitable for treating a wide range of human pain pathologies.
Vaccination of Cancer Patients Against Telomerase Induces Functional Antitumor CD8+ T Lymphocytes (2004)

These results demonstrate the immunological feasibility of vaccinating patients against telomerase and provide rationale for targeting self-antigens with critical roles in oncogenesis.
The CUP-SHAPED COTYLEDON1 gene of Arabidopsis regulates shoot apical meristem formation (2001)

In higher plants, molecular mechanisms regulating shoot apical meristem (SAM) formation and organ separation are largely unknown. The CUC1 (CUP-SHAPED COTYLEDON1) and CUC2 are functionally redundant genes that are involved in these processes. We cloned the CUC1 gene by a map-based approach, and found that it encodes a NAC-domain protein highly homologous to CUC2. CUC1 mRNA was detected in the presumptive SAM during embryogenesis, and at the boundaries between floral organ primordia. Surprisingly, overexpression of CUC1 was sufficient to induce adventitious shoots on the adaxial surface of cotyledons. Expression analyses in the overexpressor and in loss-of-function mutants suggest that CUC1 acts upstream of the SHOOT MERISTEMLESS gene.
Tauopathies: classification and clinical update on neurodegenerative diseases associated with microtubule‐associated protein tau (2006)

The majority of neurodegenerative diseases are characterized by the deposition of insoluble protein in cells of the neuromuscular system. Advances in molecular neuropathology have allowed a classification system of neurodegenerative diseases based on this protein accumulation. Microtubule-associated tau is one protein that has important functions in healthy neurons, but forms insoluble deposits in diseases now known collectively as tauopathies. Tauopathies encompass more than 20 clinicopathological entities, including Alzheimer's disease, the most common tauopathy, progressive supranuclear palsy, Pick's disease, corticobasal degeneration and post-encephalitic parkinsonism. There are important clinical, pathological, biochemical and genetic similarities in the range of these diseases and they have helped to advance our understanding of the aetiological factors that initiate neurodegeneration and tau accumulation. This review examines the important clinical features of the most prevalent tauopathies and the molecular and pathological features that underpin the classification system.
Satisfaction and Patient Experience With Sacral Neuromodulation: Results of a Single Center Sample Survey (2010)

This study shows a high satisfaction rate in patients with sacral neuromodulation. There was no relation between patient age, complaint type, therapy duration or side effects and the satisfaction rate. The number of side effects was limited but further analysis in prospective cohorts should identify patients who are likely to have side effects or stop sacral neuromodulation treatment.
Exposure to a Specific Pulsed Low‐Frequency Magnetic Field: A Double‐Blind Placebo‐Controlled Study of Effects on Pain Ratings in Rheumatoid Arthritis and Fibromyalgia Patients (2006)

These findings provide some initial support for the use of PEMF exposure in reducing pain in chronic pain populations and warrants continued investigation into the use of PEMF exposure for short-term pain relief.
PROBABILITY‐BASED INFERENCE IN COGNITIVE DIAGNOSIS (1994)

ABSTRACT Recent developments in cognitive psychology suggest models for knowledge and learning that often fall outside the realm of standard test theory. This paper concerns probability‐based inference in terms of such models. An approach utilizing Bayesian inference networks is outlined. Basic ideas of structure and computation in inference networks are discussed, and illustrated with an example from the domain of mixed‐number subtraction.