gebhart/patrepeval huggingface dataset:
Preliminary molecular genetic analysis of the Receptor Interacting Protein 140 (RIP140) in women affected by endometriosis (2005)

Our results suggest that NRIP1 gene variants, separately or in combinations, might act as predisposing factors for human endometriosis.
Neuromodulation with single‐element transcranial focused ultrasound in human thalamus (2018)

Transcranial focused ultrasound (tFUS) has proven capable of stimulating cortical tissue in humans. tFUS confers high spatial resolutions with deep focal lengths and as such, has the potential to noninvasively modulate neural targets deep to the cortex in humans. We test the ability of single-element tFUS to noninvasively modulate unilateral thalamus in humans. Participants (N = 40) underwent either tFUS or sham neuromodulation targeted at the unilateral sensory thalamus that contains the ventro-posterior lateral (VPL) nucleus of thalamus. Somatosensory evoked potentials (SEPs) were recorded from scalp electrodes contralateral to median nerve stimulation. Activity of the unilateral sensory thalamus was indexed by the P14 SEP generated in the VPL nucleus and cortical somatosensory activity by subsequent inflexions of the SEP and through time/frequency analysis. Participants also under went tactile behavioral assessment during either the tFUS or sham condition in a separate experiment. A detailed acoustic model using computed tomography (CT) and magnetic resonance imaging (MRI) is also presented to assess the effect of individual skull morphology for single-element deep brain neuromodulation in humans. tFUS targeted at unilateral sensory thalamus inhibited the amplitude of the P14 SEP as compared to sham. There is evidence of translation of this effect to time windows of the EEG commensurate with SI and SII activities. These results were accompanied by alpha and beta power attenuation as well as time-locked gamma power inhibition. Furthermore, participants performed significantly worse than chance on a discrimination task during tFUS stimulation.
Different Gene Expression Patterns in Invasive Lobular and Ductal Carcinomas of the Breast (2004)

Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) are the two major histological types of breast cancer worldwide. Whereas IDC incidence has remained stable, ILC is the most rapidly increasing breast cancer phenotype in the United States and Western Europe. It is not clear whether IDC and ILC represent molecularly distinct entities and what genes might be involved in the development of these two phenotypes. We conducted comprehensive gene expression profiling studies to address these questions. Total RNA from 21 ILCs, 38 IDCs, two lymph node metastases, and three normal tissues were amplified and hybridized to approximately 42,000 clone cDNA microarrays. Data were analyzed using hierarchical clustering algorithms and statistical analyses that identify differentially expressed genes (significance analysis of microarrays) and minimal subsets of genes (prediction analysis for microarrays) that succinctly distinguish ILCs and IDCs. Eleven of 21 (52%) of the ILCs ("typical" ILCs) clustered together and displayed different gene expression profiles from IDCs, whereas the other ILCs ("ductal-like" ILCs) were distributed between different IDC subtypes. Many of the differentially expressed genes between ILCs and IDCs code for proteins involved in cell adhesion/motility, lipid/fatty acid transport and metabolism, immune/defense response, and electron transport. Many genes that distinguish typical and ductal-like ILCs are involved in regulation of cell growth and immune response. Our data strongly suggest that over half the ILCs differ from IDCs not only in histological and clinical features but also in global transcription programs. The remaining ILCs closely resemble IDCs in their transcription patterns. Further studies are needed to explore the differences between ILC molecular subtypes and to determine whether they require different therapeutic strategies.
Nogo-A Interacts with the Nogo-66 Receptor through Multiple Sites to Create an Isoform-Selective Subnanomolar Agonist (2005)

Nogo is a myelin-derived protein that limits axonal regeneration after CNS injury. A short hydrophilic Nogo-66 loop between two hydrophobic domains of Nogo binds to a Nogo-66 receptor (NgR) to inhibit axonal outgrowth. Inhibition of axon outgrowth and cell spreading by a second Nogo domain, termed Amino-Nogo-A, is thought to be mediated by a distinct receptor complex. Here, we define a novel Nogo-A-specific domain in Amino-Nogo that binds to NgR with nanomolar affinity. This second domain of 24 amino acids does not alter cell spreading or axonal outgrowth. Fusion of the two NgR-binding Nogo-A domains creates a ligand with substantially enhanced affinity for NgR and converts a NgR antagonist peptide to an agonist. Thus, NgR activation by Nogo-A involves multiple sites of interaction between Nogo-A and NgR.
[Aspects of progesterone receptor (PR) activity regulation - impact on breast cancer progression]. (2015)

Progesterone receptor (PR) and its specific ligand play a key role in development and physiology of mammary gland. The role of PR in initiation and progression of breast carcinoma (BCa) is unquestionable, although molecular mechanism of PR action is complex and not fully understood. It is known that increased risk of breast cancer is associated with progestin-based (synthetic ligands of progesterone) hormonal contraception or hormone replacement therapies. It is estimated that ER/PR-positive tumours represent approximately 50-70% of all BCa cases, and the loss of PR is associated with resistance to hormonal therapy and increased tumour invasiveness. In classical, genomic signalling pathway cytoplasmic PR, following ligand binding, translocates to the nucleus and regulates expression of genes with the PRE sequence. PR is also involved in a large number of alternative, non-genomic signalling cascades, e.g. PR is able to activate MAPK and PI3K/AKT pathways, which leads to regulation of gene expression. The cross-talk between PR and Growth Factors Receptors (GFR) results in progesterone-independent activation of PR as well as PR-regulated GFR expression and activation. Growth factors signalling promotes formation of a pool of hypersensitive PR responsive to even very low ligand concentration. Transcriptional activity of PR as well as its dynamic impact on processes such as cell migration and adhesion are crucial for BCa progression. Further studies of multifaceted mechanisms of PR action may contribute to new PR-targeting therapeutic strategies for breast cancer patients.
Localization and dynamics of small circular DNA in live mammalian nuclei (2004)

While genomic DNA, packaged into chromatin, is known to be locally constrained but highly dynamic in the nuclei of living cells, little is known about the localization and dynamics of small circular DNA molecules that invade cells by virus infection, application of gene therapy vectors or experimental transfection. To address this point, we have created traceable model substrates by direct labeling of plasmid DNA with fluorescent peptide nucleic acids, and have investigated their fate after microinjection into living cells. Here, we report that foreign DNA rapidly undergoes interactions with intranuclear structural sites that strongly reduce its mobility and restrict the DNA to regions excluding nucleoli and nuclear bodies such as PML bodies. The labeled plasmids partially co-localize with SAF-A, a well characterized marker protein for the nuclear 'scaffold' or 'matrix', and are resistant towards extraction by detergent and, in part, elevated salt concentrations. We show that the localization and the low mobility of plasmids is independent of the plasmid sequence, and does not require the presence of either a scaffold attachment region (SAR) DNA element or a functional promoter.
A 193-Amino Acid Fragment of the SARS Coronavirus S Protein Efficiently Binds Angiotensin-converting Enzyme 2 (2004)

The coronavirus spike (S) protein mediates infection of receptor-expressing host cells and is a critical target for antiviral neutralizing antibodies. Angiotensin-converting enzyme 2 (ACE2) is a functional receptor for the coronavirus (severe acute respiratory syndrome (SARS)-CoV) that causes SARS. Here we demonstrate that a 193-amino acid fragment of the S protein (residues 318-510) bound ACE2 more efficiently than did the full S1 domain (residues 12-672). Smaller S protein fragments, expressing residues 327-510 or 318-490, did not detectably bind ACE2. A point mutation at aspartic acid 454 abolished association of the full S1 domain and of the 193-residue fragment with ACE2. The 193-residue fragment blocked S protein-mediated infection with an IC(50) of less than 10 nm, whereas the IC(50) of the S1 domain was approximately 50 nm. These data identify an independently folded receptor-binding domain of the SARS-CoV S protein.
A combined approach for QoS-guaranteed and low-power video decoding (2011)

This paper proposes a power management technique for video playback in mobile multimedia devices, which combines low-power video decoding and QoS-guaranteed algorithms: ILI (Interval-based Linear Interpolation) and QLB (QoS-guaranteed and Low-power Buffering). First, the proposed ILI algorithm precisely estimates the decoding time of video frames through interval-based linear interpolation. Second, the QLB algorithm has two modes of operation, and dynamically switches between the modes based on feedback of decoding statistics of recent frames. The combinations ILI and QLB algorithms allow the CPU voltage and clock frequency to be adjusted to the optimal setting. Our extensive experiments show that the proposed approach can achieve about 4.8%-13.7% more power savings compared with existing methods.
Advanced Technologies for Gastrointestinal Endoscopy (2012)

The gastrointestinal tract is home to some of the most deadly human diseases. Exacerbating the problem is the difficulty of accessing it for diagnosis or intervention and the concomitant patient discomfort. Flexible endoscopy has established itself as the method of choice and its diagnostic accuracy is high, but there remain technical limitations in modern scopes, and the procedure is poorly tolerated by patients, leading to low rates of compliance with screening guidelines. Although advancement in clinical endoscope design has been slow in recent years, a critical mass of enabling technologies is now paving the way for the next generation of gastrointestinal endoscopes. This review describes current endoscopes and provides an overview of innovative flexible scopes and wireless capsules that can enable painless endoscopy and/or enhanced diagnostic and therapeutic capabilities. We provide a perspective on the potential of these new technologies to address the limitations of current endoscopes in mass cancer screening and other contexts and thus to save many lives.
Silencing of a meristematic gene using geminivirus‐derived vectors (2001)

Geminiviruses are DNA viruses that replicate and transcribe their genes in plant nuclei. They are ideal vectors for understanding plant gene function because of their ability to cause systemic silencing in new growth and ease of inoculation. We previously demonstrated DNA episome-mediated gene silencing from a bipartite geminivirus in Nicotiana benthamiana. Using an improved vector, we now show that extensive silencing of endogenous genes can be obtained using less than 100 bp of homologous sequence. Concomitant symptom development varied depending upon the target gene and insert size, with larger inserts producing milder symptoms. In situ hybridization of silenced tissue in attenuated infections demonstrated that silencing occurs in cells that lack detectable levels of viral DNA. A mutation confining the virus to vascular tissue produced extensive silencing in mesophyll tissue, further demonstrating that endogenous gene silencing can be separated from viral infection. We also show that two essential genes encoding a subunit of magnesium chelatase and proliferating cell nuclear antigen (PCNA) can be silenced simultaneously from different components of the same viral vector. Immunolocalization of silenced tissue showed that the PCNA protein was down-regulated throughout meristematic tissues. Our results demonstrate that geminivirus-derived vectors can be used to study genes involved in meristem function in intact plants.
Advancements in Noncontact, Multiparameter Physiological Measurements Using a Webcam (2010)

We present a simple, low-cost method for measuring multiple physiological parameters using a basic webcam. By applying independent component analysis on the color channels in video recordings, we extracted the blood volume pulse from the facial regions. Heart rate (HR), respiratory rate, and HR variability (HRV, an index for cardiac autonomic activity) were subsequently quantified and compared to corresponding measurements using Food and Drug Administration-approved sensors. High degrees of agreement were achieved between the measurements across all physiological parameters. This technology has significant potential for advancing personal health care and telemedicine.
An H/ACA guide RNA directs U2 pseudouridylation at two different sites in the branchpoint recognition region in Xenopus oocytes (2002)

U2 is the most extensively modified of all spliceosomal snRNAs. We previously showed that at least some of the internally modified nucleotides in U2 snRNA are required for snRNP biogenesis and pre-mRNA splicing. Recent work from several laboratories suggests that nuclear guide RNAs facilitate U2 snRNA internal modification, including pseudouridylation and 2'-O-methylation. Here, we present a novel approach to identifying guide RNAs for U2 pseudouridylation. Several Xenopus oocyte nuclear RNAs were affinity selected with U2 snRNA substituted with 5-fluorouridine, a pseudouridylation inhibitor that sequesters pseudouridylases. One of these RNAs was sequenced and found to be a novel RNA of 134 nt. This small RNA contains an H/ACA motif and folds into a typical H/ACA RNA structure, and its authenticity as an H/ACA RNA was confirmed by immunoprecipitation analysis. The RNA contains two guide sequences for pseudouridylation (psi) of U2 snRNA at positions 34 and 44 in the branch-site recognition region, and we demonstrate that this RNA indeed guides the formation of psi34 and psi44 in U2 using a Xenopus oocyte reconstitution system. Therefore, this novel RNA was designated pugU2-34/44, for pseudouridylation guide for U2 snRNA U34 and U44. Intranuclear localization analyses indicate that pugU2-34/44 resides within the nucleoplasm rather than nucleoli or Cajal bodies where other guide RNAs have been localized. Our results clarify the mechanism of U2 snRNA pseudouridylation in Xenopus oocytes, and have interesting implications with regard to the intranuclear localization of U2 snRNA pseudouridylation.
Structural Origins of High-Affinity Biotin Binding to Streptavidin (1989)

The high affinity of the noncovalent interaction between biotin and streptavidin forms the basis for many diagnostic assays that require the formation of an irreversible and specific linkage between biological macromolecules. Comparison of the refined crystal structures of apo and a streptavidin:biotin complex shows that the high affinity results from several factors. These factors include the formation of multiple hydrogen bonds and van der Waals interactions between biotin and the protein, together with the ordering of surface polypeptide loops that bury the biotin in the protein interior. Structural alterations at the biotin binding site produce quaternary changes in the streptavidin tetramer. These changes apparently propagate through cooperative deformations in the twisted beta sheets that link tetramer subunits.
An experimental study of bibliographic coupling between technical papers (Corresp.) (1963)

Abstract : A single item of reference shared by two papers is defined as a unit of coupling between them. Based on this unit, two graded criteria of coupling are defined. These are applied to a test population of papers to generatepers, by M. M. Kessler. 21 Nov 61, rev. 15 June 62, 10p. incl. tables, 3 refs. (In cooperation with National Science Foundatio ) Unclassified report DESCRIPTORS: *Scientific reports, Documenta tion, Statistical analysis, Periodicals.A single item of reference shared by two papers is defined as a unit of coupling between them. Based on this unit, two graded criteria of coupling are defined. These are applied to a test population of papers to generate smaller related groups. The process was tested manually with results that encourage mdy of bibliographic coupling between technical papers.
Megavoltage CT on a tomotherapy system (1999)

A megavoltage computed tomography (MVCT) system was developed on the University of Wisconsin tomotherapy benchtop. This system can operate either axially or helically, and collect transmission data without any bounds on delivered dose. Scan times as low as 12 s per slice are possible, and scans were run with linac output rates of 100 MU min(-1), although the system can be tuned to deliver arbitrarily low dose rates. Images were reconstructed with clinically reasonable doses ranging from 8 to 12 cGy. These images delineate contrasts below 2% and resolutions of 3.0 mm. Thus, the MVCT image quality of this system should be sufficient for verifying the patient's position and anatomy prior to radiotherapy. Additionally, synthetic data were used to test the potential for improved MVCT contrast using maximum-likelihood (ML) reconstruction. Specifically, the maximum-likelihood expectation-maximization (ML-EM) algorithm and a transmission ML algorithm were compared with filtered backprojection (FBP). It was found that for expected clinical MVCT doses enough imaging photons are used such that little benefit is conferred by the improved noise model of ML algorithms. For significantly lower doses, some quantitative improvement is achieved through ML reconstruction. Nonetheless, the image quality at those lower doses is not satisfactory for radiotherapy verification.
Fluid Shear Stress Activation of IκB Kinase Is Integrin-dependent (1998)

Vascular endothelial cells (ECs), forming a boundary between the circulating blood and the vessel wall, are constantly subjected to fluid shear stress due to blood flow. The aim of this study was to determine the role of the recently identified IkappaB kinases (IKKs) in shear stress activation of NF-kappaB and to elucidate the upstream signaling mechanism that mediates IKK activation. Our results demonstrate that IKKs in ECs are activated by shear stress in a rapid and transient manner. This IKK activation is followed by IkappaB degradation and NF-kappaB translocation into the nucleus. Transfection of plasmids encoding catalytic inactive mutants of IKKs, i.e. hemagglutinin (HA)-IKKalpha(K44M) and HA-IKKbeta(K44A), inhibits shear stress-induced NF-kappaB translocation. In addition, constructs encoding antisense IKKs, i.e. HA-IKKalpha(AS) and HA-IKKbeta(AS), attenuate shear stress induction of a promoter driven by the kappaB enhancer element. Preincubation of the EC monolayer with a monoclonal anti-alphavbeta3 integrin antibody (clone LM609) attenuates shear stress induction of IKK. Inhibition of tyrosine kinases by genistein causes a similar down-regulating effect. These results suggest that the integrin-mediated signaling pathway regulates NF-kappaB through IKKs in ECs in response to shear stress.
An experimental multi-media bridging system (1988)

The prototype system, which is described in this paper and called the Multi-Media Bridge, is designed to test service concepts and evolving technologies that make possible the deployment of multi-media group communications in future broadband networks. It incorporates such features as extended quality audio, full-motion video, graphics and data multi-point communications capability. The Bridge could serve as either a separate vendor entity or as an integral part of a network-based complex. The multi-shelf architecture of the experimental system allows a variety of technical problems and issues to be autonomously addressed. The shelves, designated Audio, Video, Graphics, and Data, are functionally integrated by a distributed control capability. A graphics user interface was developed which can be realized on any PC or workstation that supports the MIT X-Windowing system. It provides users with the flexibility to dynamically invoke each medium at any time and control various modes of media integration.
Assessment of Spermatozoal Function Using Dual Fluorescent Staining and Flow Cytometric Analyses1 (1986)

Spermatozoa from bulls, boars, dogs, horses, mice, and men were examined using a fluorogenic stain consisting of the membrane-permeant substrate carboxyfluorescin diacetate (CFDA) and the relatively membrane-impermeant nuclear stain propidium iodide (PI). Three distinct populations of spermatozoa were discernible in samples from each species upon microscopic examination. Individual spermatozoa, presumed to be viable because of their motility, retained products of the fluorescein chromophore throughout the cell. A second population of spermatozoa in which the nuclei stained red with PI retained the green fluorescein fluorophore mainly in the acrosome. A third population, presumed to be degenerate spermatozoa, possessed only red fluorescent nuclei. These populations were quantified using dual parameter flow cytometry in 14 samples of cryopreserved bovine spermatozoa for which fertility and seminal quality data were available. Flow cytometric analyses were highly correlated with other seminal quality measurements. Sequential flow cytometric analyses provided the ability to rapidly quantitate changes in specific fluorescently stained populations. The ability to make rapid quantitative measurements should allow development of new and presumably more reliable information on the functional aspects of spermatozoa.
The SCID-hu Mouse: Murine Model for the Analysis of Human Hematolymphoid Differentiation and Function (1988)

The study of human hematopoietic cells and the human immune system is hampered by the lack of a suitable experimental model. Experimental data are presented showing that human fetal liver hematopoietic cells, human fetal thymus, and human fetal lymph node support the differentiation of mature human T cells and B cells after engraftment into mice with genetically determined severe combined immunodeficiency. The resultant SCID-hu mice are found to have a transient wave of human CD4+ and CD8+ T cells and human IgG (immunoglobulin G) in the peripheral circulation. The functional status of the human immune system within this mouse model is not yet known.
Reducing the branch penalty in pipelined processors (1988)

A probabilistic model is developed to quantify the performance effects of the branch penalty in a typical pipeline. The branch penalty is analyzed as a function of the relative number of branch instructions executed and the probability that a branch is taken. The resulting model shows the fraction of maximum performance achievable under the given conditions. Techniques to reduce the branch penalty include static and dynamic branch prediction, the branch target buffer, the delayed branch, branch bypassing and multiple prefetching, branch folding, resolution of branch decision early in the pipeline, using multiple independent instruction streams in a shared pipeline, and the prepare-to-branch instruction.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>