gebhart/patrepeval huggingface dataset:
Locked 2′-Deoxy-2′,4′-Difluororibo Modified Nucleic Acids: Thermal Stability, Structural Studies, and siRNA Activity (2015)

2'-Deoxy-2',4'-difluorouridine (2',4'-diF-rU) was readily incorporated into DNA and RNA oligonucleotides via standard solid phase synthesis protocols. NMR and thermal denaturation (Tm) data of duplexes was consistent with the 2',4'-diF-rU nucleotides adopting a rigid North (RNA-like) sugar conformation, as previously observed for the nucleoside monomer. The impact of this modification on Tm is neutral when incorporated within RNA:RNA duplexes, mildly destabilizing when located in the RNA strand of a DNA:RNA duplex, and highly destabilizing when inserted in the DNA strand of DNA:RNA and DNA:DNA duplexes. Molecular dynamics calculations suggest that the destabilization effect in DNA:DNA and DNA:RNA duplexes is the result of structural distortions created by A/B junctions within the helical structures. Quantum mechanics calculations suggest that the "neutral" effect imparted to A-form duplexes is caused by alterations in charge distribution that compensate the stabilizing effect expected for a pure North-puckered furanose sugar. 2',4'-diF-RNA modified siRNAs were able to trigger RNA interference with excellent efficiency. Of note, incorporation of a few 2',4'-diF-rU residues in the middle of the guide (antisense) strand afforded siRNAs that were more potent than the corresponding siRNAs containing LNA and 2'-F-ANA modifications, and as active as the 2'-F-RNA modified siRNAs.
Characteristics of focused beam spots using negative ion beams from a compact surface plasma source and merits for new applications (1998)

The characteristics of H− beams from a compact Penning-type surface plasma source have been studied with the goal of evaluating their merits for improved focused ion beam (FIB) systems. As a proof-of-the principles experiment to demonstrate the beam quality a simple, prototype source was developed without any special cooling arrangement of the electrodes. The source is operated in a pulsed mode with a maximum duty factor of 1%; and the operation can be extended to the dc mode by using water cooling. The beam brightness is estimated to be ∼0.5×105 A cm2 sr−1 at a beam energy of 7 kV, and the energy spread of the beam for angular beam intensity of ∼40 mA/sr is ⩽3 eV. The beam at an energy of 7 keV has been focused by a lens with a magnification factor of M∼0.1, and the spot size is determined by scanning a Si knife edge over the beam as well as by poly(methylmethacrylate) resist exposures. A focused spot, with diameter of ∼6 μm and current density of ∼10 mA/cm2, has been achieved. The dependence of the spot characteristics with the beam intensity from the source has been studied. The results suggest that a submicron size spot with a current density of ⩾1 A/cm2 can be generated using these beams for M∼0.01. The source, with its simple, robust technology, seems an attractive choice for FIB applications.
Host-virus interaction: a new role for microRNAs (2006)

MicroRNAs (miRNAs) are a new class of 18-23 nucleotide long non-coding RNAs that play critical roles in a wide spectrum of biological processes. Recent reports also throw light into the role of microRNAs as critical effectors in the intricate host-pathogen interaction networks. Evidence suggests that both virus and hosts encode microRNAs. The exclusive dependence of viruses on the host cellular machinery for their propagation and survival also make them highly susceptible to the vagaries of the cellular environment like small RNA mediated interference. It also gives the virus an opportunity to fight and/or modulate the host to suite its needs. Thus the range of interactions possible through miRNA-mRNA cross-talk at the host-pathogen interface is large. These interactions can be further fine-tuned in the host by changes in gene expression, mutations and polymorphisms. In the pathogen, the high rate of mutations adds to the complexity of the interaction network. Though evidence regarding microRNA mediated cross-talk in viral infections is just emerging, it offers an immense opportunity not only to understand the intricacies of host-pathogen interactions, and possible explanations to viral tropism, latency and oncogenesis, but also to develop novel biomarkers and therapeutics.
Structure, subnuclear distribution, and nuclear matrix association of the mammalian telomeric complex. (1996)

Mammalian telomeres are composed of long arrays of TTAGGG repeats complexed with the TTAGGG repeat binding factor, TRF. Biochemical and ultrastructural data presented here show that the telomeric DNA and TRF colocalize in individual, condensed structures in the nuclear matrix. Telomeric TTAGGG repeats were found to carry an array of nuclear matrix attachment sites occurring at a frequency of at least one per kb. The nuclear matrix association of the telomeric arrays extended over large domains of up to 20-30 kb, encompassing the entire length of most mammalian telomeres. TRF protein and telomeric DNA cofractionated in nuclear matrix preparations and colocalized in discrete, condensed sites throughout the nuclear volume. FISH analysis indicated that TRF is an integral component of the telomeric complex and that the presence of TRF on telomeric DNA correlates with the compact configuration of telomeres and their association with the nuclear matrix. Biochemical fractionation of TRF and telomeric DNA did not reveal an interaction with the nuclear lamina. Furthermore, ultrastructural analysis indicated that the mammalian telomeric complex occupied sites throughout the nuclear volume, arguing against a role for the nuclear envelope in telomere function during interphase. These results are consistent with the view that mammalian telomeres form nuclear matrix-associated, TRF-containing higher order complexes at dispersed sites throughout the nuclear volume.
Effectiveness of Cognitive Skill Remediation in Acute Stroke Patients (1983)

The purpose of this study was to determine whether a cognitive skills remediation program could help acute stroke patients regain important thinking skills. Patients in a community hospital stroke program were pre-tested in three skill areas--visual scanning, visual-spatial orientation, and time judgment--and randomly assigned to a treatment (n = 16) or control (n = 17) group. The treatment group received cognitive skill retraining on a one-to-one basis for 30 minutes per day, 3 days per week, for 3 weeks. The retraining involved the use of paper and pencil tasks, simple cuing procedures, positive reinforcement, and immediate feedback. Although the control group did not receive this treatment, conventional therapies continued for both groups. Patients receiving treatment had overall and separate skill improvement scores that were significantly higher than those for control patients. The implications of this type of treatment program are discussed.
Correlation of Intra-Articular Ankle Pathology with Cytokine Biomarkers and Matrix Degradation Products (2012)

These tests may play a role in determining the necessity for arthroscopy or intra-articular procedures in equivocal candidates.
Next‐Generation Sequencing of MicroRNAs for Breast Cancer Detection (2011)

It is reported that different microRNA (miRNA) profiles can be detected in the blood of cancer patients. We investigated that whether the key serum miRNAs could discriminate patients with and without breast cancer. This study was divided into three parts: (1) miRNA marker discovery using SOLiD sequencing-based miRNA profiling on cancerous and adjacent noncancerous breast tissue of one breast cancer patient; (2) marker selection and validation by real-time PCR on a small set of serum; (3) gene ontology analysis of the key miRNA target genes. Of genome-wide tissue miRNA expression analysis, five miRNAs were found to be altered more than fivefold by SOLiD sequencing (i.e., miR-29a, miR-23a, miR-23b, miR-192, and miR-21). All the five miRNAs were validated on the 20 breast cancer patients and 20 controls. miR-29a and miR-21 were significantly increased in the serum of breast cancer patients (P < .05). Gene ontology analysis of the target genes revealed enrichment for special biological process categories, that is, signal transduction, development, apoptosis, cell proliferation, and cell adhesion. SOLiD sequencing provides a promising method for cancer-related miRNA profiling. Serum miRNAs may be useful biomarkers for breast cancer detection.
Does the Metabolic Syndrome Improve Identification of Individuals at Risk of Type 2 Diabetes and/or Cardiovascular Disease? (2004)

The metabolic syndrome is inferior to established predicting models for either type 2 diabetes or CVD.
Bioengineered Skin Constructs and Their Use in Wound Healing (2011)

The advances that have occurred in testing and proving the efficacy of bioengineered skin hold great promise for further improvements in the way this technology is used in the surgical field and in wound care. Advances in therapeutic agents have also led to greater understanding of pathophysiology. Thus, wound bed preparation as a concept and as an approach is in fact the result of the need to maximize the benefits of advanced therapies.
Solution‐Phase Parallel Synthesis of an N‐Alkylated Dihydropteridinone Library from Fluorous Amino Acids. (2005)

Abstract For Abstract see ChemInform Abstract in Full Text.
Organic Long‐Persistent Luminescence: Many Exciplex Systems Exhibit Organic Long‐Persistent Luminescence (Adv. Funct. Mater. 22/2020) (2020)

In article number 2000795, Ryota Kabe, Chihaya Adachi, and co-workers show that many exciplex systems exhibit afterglow emission because of the charge separation event during photoexcitation. The emission pathway and color of organic long-persistent luminescence can be controlled by the relationship between the local excited states and charge-transfer excited states of materials.
Enhancing Supervised Learning with Unlabeled Data (2000)

In many practical learning scenarios, there is a small amount of labeled data along with a large pool of unlabeled data. Many supervised learning algorithms have been developed and extensively studied. We present a new &amp;quot;co-training&amp;quot; strategy for using unlabeled data to improve the performance of standard supervised learning algorithms. Unlike much of the prior work, such as the co-training procedure of Blum and Mitchell (1998), we do not assume there are two redundant views both of which are sufficient for perfect classification. The only requirement our co-training strategy places on each supervised learning algorithm is that its hypothesis partitions the example space into a set of equivalence classes (e.g. for a decision tree each leaf defines an equivalence class). We evaluate our co-training strategy via experiments using data from the UCI repository. 1. Introduction In many practical learning scenarios, there is a small amount of labeled data along with a lar...
Effect of the Normal Microbial Flora on the Resistance of the Small Intestine to Infection (1966)

Abrams, Gerald D. (The University of Michigan Medical School, Ann Arbor), and Jane E. Bishop. Effect of the normal microbial flora on the resistance of the small intestine to infection. J. Bacteriol. 92:1604-1608. 1966.-Mucosal structure in the small intestine is known to be influenced by the normal microbial flora. This suggests that mucosal resistance to invasion by enteric pathogens might also be affected by the flora. To assess this possibility, germ-free and conventional mice were challenged with Salmonella typhimurium, and both the growth of organisms within the intestinal lumen and the translocation to mesenteric lymph nodes were studied quantitatively. There were significantly more organisms 24 hr after intragastric challenge in the mesenteric nodes of germ-free animals than in those of conventional ones. However, since intraluminal growth in the intestine was also greater in germ-free animals, no conclusion could be drawn about mucosal resistance per se. Results were similar when the challenge was intraduodenal. However, when intestinal emptying was prevented by ileal ligation before challenge, both intraluminal growth and translocation of S. typhimurium were equal in the two groups of mice. It is concluded from these data, as well as from preliminary dye studies of intestinal motility, that the normal flora does not influence mucosal resistance directly, but may alter enteric infection by affecting intestinal emptying.
One drop at a time: toward droplet microfluidics as a versatile tool for single-cell analysis (2014)

Miniaturization has been the key driver for many remarkable technological developments in recent decades. Miniaturization has now also extended into biology, thereby setting the stage for high-throughput single-cell analysis. This advancement is important because, despite detailed molecular information on individual cell subtypes, virtually no information is available on the functional capacities of individual cells. Typical in vivo animal models, as well as in vitro laboratory test tube experiments, only yield a global outcome of interactions of often millions of cells rather than providing insight into the functional contribution of individual cells. Reaction volumes of biological experiments have generally been reduced from milliliters to microliters. Tools and methods that study single-cell behavior have become increasingly important, but often do not allow for high-throughput manipulation. Recent advances in (droplet-based) microfluidics enable systematic high-throughput analyses of individual cells in a highly controlled manner. The implementation of microfluidic technologies in single-cell analysis is one of the most promising approaches that not only offers new information and high-throughput screening but also enables the creation of innovative conditions that are impractical or impossible by conventional methods. In this review, we provide a comprehensive overview of recent developments in droplet-based microfluidics for single-cell studies. Applying droplet microfluidics to cells trapped within water-in-oil droplets offers a powerful way to study single cells in action. Wilhelm Huck and colleagues at Radboud University in the Netherlands have reviewed the application of this technique and research toward the study of individual cells. Unlike most cell analysis methods, it allows specific chemicals to be associated with the individual cell they come from or interact with. Researchers are currently addressing many technical challenges, including performing washing steps inside droplets and developing better ways to monitor and manipulate the cells at high-throughput rates. Current work is focused on reducing the complexity and enhancing the sensitivity of the technique. The authors also review applications that could soon become routine, including drug and antibody studies, tracking single-cell gene expression, studies of cell evolution and analysis of cellular interactions when droplets fuse. This review highlights the recent advances in droplet-based microfluidics for studying the properties of single cells, with a specific interest in quantitative studies into the heterogeneity of large populations of cells
Effect of First-Line Chemotherapy Combined With Cetuximab or Bevacizumab on Overall Survival in Patients With KRAS Wild-Type Advanced or Metastatic Colorectal Cancer (2017)

clinicaltrials.gov identifier: NCT00265850.
The Bottleneck in the Cancer Biomarker Pipeline and Protein Quantification through Mass Spectrometry–Based Approaches: Current Strategies for Candidate Verification (2009)

Although it is unlikely that MS-based protein quantification will replace immunoassays in the near future, with the expected improvements in limits of detection and specificity in instrumentation, MRM-based approaches show great promise for alleviating the existing bottleneck to discovery.
PCR-based high-risk HPV test in cervical cancer screening gives objective risk assessment of women with cytomorphologically normal cervical smears (1996)

Cervical-cancer screening programmes using cytomorphological criteria could be more efficient if the screening included objective individual risk factors for women with normal cytology, such as a test for high-risk human papillomavirus (HPV). The value of a PCR-based test for high-risk HPV types was studied in a cohort of 1622 women presenting in a routine triannual population-based screening programme. Women were included in the study when they had no previous history of cervical dysplasia; and their initial Pap smear was read as normal (Pap 1 or 2). The mean age of the women was 42 years (range 34-54 years) and mean follow-up time was 40 months (range 5-73 months). Women were referred for colposcopically directed biopsies if they had had 2 successive cervical smears read as Pap 3a (mild to moderate dyskaryosis) or one read as > or = Pap 3b (severe dyskaryosis). Women with histologically confirmed cervical intraepithelial neoplasia grade III (CIN III) were considered positive cases. All women were tested for 14 high-risk HPV genotypes. Of the 86 high-risk HPV-positive women, 6 developed CIN III, whereas only 1 of the 1536 HPV-negative women did. The women with normal Pap smears containing high-risk HPV genotypes were 116 times (95% CI, 13-990) more at risk of developing CIN III, in contrast to women without high-risk HPV. These results support the view that the interval between successive smears in cervical-cancer screening can be increased considerably for women with cytomorphologically normal and high-risk HPV-negative cervical smears as determined by PCR.
A novel protein domain required for apoptosis. Mutational analysis of human Fas antigen (1993)

The Fas antigen is a cell surface protein that can mediate apoptosis and that belongs to the tumor necrosis factor receptor family. Murine fibroblast L929 cells or T-cell lymphoma WR19L cells expressing the human Fas antigen were killed within 4-6 h by anti-human Fas antibody in a concentration-dependent manner. Human Fas antigen cDNAs with various mutations in the cytoplasmic region were constructed and expressed in L929 cells. A deletion of 15 amino acids from the C terminus of the Fas antigen enhanced the Fas antibody-induced killing activity, whereas a further deletion abolished its activity. This suggests the presence of an inhibitory as well as a signal-transducing domain in the cytoplasmic region of the Fas antigen. A 68-amino acid portion of the signal-transducing domain significantly conserved in the Fas antigen as well as in the type I tumor necrosis factor receptor was considered to be the novel protein domain required for apoptotic signal transduction.
Pharmacophores for Ligand Recognition and Activation / Inactivation of the Cannabinoid Receptors (2003)

The cannabinoid CB(1) and CB(2) receptors belong to the Class A, rhodopsin-like family of G protein-coupled receptors. Antagonists for each receptor sub-type, as well as four structural classes of agonists that bind to both receptors, have been identified. An extensive amount of SAR has been developed for agonists and antagonists that bind at CB1, while the SAR of CB2 ligands is only now emerging in the literature. Cannabinoid agonists have been suggested to have potential therapeutic uses as appetite stimulants, analgesics, anti-emetics, anti-diarrheals, anti-spasmodics, tumor anti-proliferative agents, anti-glaucoma agents and as agents for the treatment of diseases associated with inappropriate retention of aversive memories such as post-traumatic stress disorders and phobias. Cannabinoid CB1 antagonists have been suggested to have potential therapeutic uses as appetite suppressants and as agents that improve memory. This review focuses first on recent CB1 and CB2 SAR and on the pharmacophores that have been developed for ligand recognition at the CB1 receptor. Emerging ideas about how the cannabinoid receptors are activated by agonists or inactivated by inverse agonists are then presented. Challenges for future SAR and pharmacophore development are also identified.
Acoustic field characterization of a clinical magnetic resonance‐guided high‐intensity focused ultrasound system inside the magnet bore (2017)

The proposed hydrophone measurement technique offers a convenient and reliable method for characterizing the acoustic fields of clinical MR-HIFU systems inside the magnet bore. The technique was validated for use by measurements outside the MRI suite using a standard hydrophone calibration technique. This technique can be a useful tool in MR-HIFU quality assurance and acoustic field assessment.
Selective O-Allylation of Amidoalcohols on Solid Support (1996)

Selective O-allylation of non-activated primary alcohols in the presence of amide function is achieved by adsorption on the surface of chromatographic alumina. Microwave irradiation enhances considerably the rate of these reactions.
Ferroportin residue C326 is critical for its interaction with hepcidin (2008)

The hormone hepcidin binds to the Fe exporter Fpn and induces its internalization and degradation, decreasing Fe efflux from cells into plasma. Fpn mutations that confer resistance to hepcidin cause classical hemochromatosis with parenchymal Fe loading. We analyzed mutations C326S, C326T, N144D and N144T to address the mechanism of Fpn interaction with hepcidin. Human Fpn‐EGFP construct was subjected to site‐directed mutagenesis and analyzed in HEK293T cells. The Fpn mutants localized properly to the cell surface and exported Fe normally. However, they were either completely (C326S/T) or partially (N144D/T) resistant to hepcidin‐mediated internalization, and exported Fe even in the presence of hepcidin. 125I‐hepcidin binding was completely (C236S/T) or partially (N144D/T) abrogated. C326 and C205 were reported to be cell surface thiols. A non‐permeable thiol‐dependent crosslinker linked hepcidin to Fpn but not in C326S/T mutants, and only partly in N144D/T mutants. Alkylation of Fpn‐expressing cells ablated 125I‐hepcidin binding. We next examined whether hepcidin binding depended on a transient SS‐bond formation between C205 and C326. C205S/T substitutions, however, only partially inhibited hepcidin uptake and crosslinking. Bacitracin had no effect on hepcidin uptake or Fpn internalization indicating that isomerisation of a C205‐C326 disulfide bond was not necessary. Thus the C326 thiol is located in or near the binding site of hepcidin and is essential for hepcidin binding and subsequent internalization of ferroportin. Our observations help explain the severity of hemochromatosis in patients with C326X mutations.