gebhart/patrepeval huggingface dataset:
Tumour macrophages as potential targets of bisphosphonates (2011)

Tumour cells communicate with the cells of their microenvironment via a series of molecular and cellular interactions to aid their progression to a malignant state and ultimately their metastatic spread. Of the cells in the microenvironment with a key role in cancer development, tumour associated macrophages (TAMs) are among the most notable. Tumour cells release a range of chemokines, cytokines and growth factors to attract macrophages, and these in turn release numerous factors (e.g. VEGF, MMP-9 and EGF) that are implicated in invasion-promoting processes such as tumour cell growth, flicking of the angiogenic switch and immunosuppression. TAM density has been shown to correlate with poor prognosis in breast cancer, suggesting that these cells may represent a potential therapeutic target. However, there are currently no agents that specifically target TAM's available for clinical use.Bisphosphonates (BPs), such as zoledronic acid, are anti-resorptive agents approved for treatment of skeletal complication associated with metastatic breast cancer and prostate cancer. These agents act on osteoclasts, key cells in the bone microenvironment, to inhibit bone resorption. Over the past 30 years this has led to a great reduction in skeletal-related events (SRE's) in patients with advanced cancer and improved the morbidity associated with cancer-induced bone disease. However, there is now a growing body of evidence, both from in vitro and in vivo models, showing that zoledronic acid can also target tumour cells to increase apoptotic cell death and decrease proliferation, migration and invasion, and that this effect is significantly enhanced in combination with chemotherapy agents. Whether macrophages in the peripheral tumour microenvironment are exposed to sufficient levels of bisphosphonate to be affected is currently unknown. Macrophages belong to the same cell lineage as osteoclasts, the major target of BPs, and are highly phagocytic cells shown to be sensitive to bisphosphonates in model studies; In vitro, zoledronic acid causes increased apoptotic cell death; in vivo the drug has been shown to inhibit the production of pro-angiogenic factor MMP-9, as well as most recent evidence showing it can trigger the reversal of the TAMs phenotype from pro-tumoral M2 to tumoricidal M1. There is thus accumulating evidence supporting the hypothesis that effects on TAMs may contribute to the anti-tumour effect of bisphosphonates. This review will focus in detail on the role of tumour associated macrophages in breast cancer progression, the actions of bisphosphonates on macrophages in vitro and in tumour models in vivo and summarise the evidence supporting the potential for the targeting of tumour macrophages with bisphosphonates.
Symmetry based indexing of diatoms in an image database (2002)

We introduce several methods for symmetry detection and present results of their experimental evaluation on diatom images. The methods are based on distance lists, cyclic string matching, and gray level gradient direction histograms. From the experimental results it can be concluded that symmetry information is useful for various indexing tasks in image databases. Types of symmetry considered in this paper are rotational and reflectional symmetry of the shape as well as symmetry of the gray level distribution of the internal structure of objects. Using the symmetry based indexing scheme proposed, the effort for the subsequent task of diatom classification can significantly be reduced.
Schizophrenia: An Epigenetic Puzzle? (1999)

Developments in molecular biology over the past three decades have led to an increasing awareness of the importance of epigenetic phenomena in a variety of genome functions. Epigenetic aspects of complex multifactorial diseases including schizophrenia, however, have not been investigated sufficiently. Various facets of epigenetics are reevaluated through their putative relevance to four theories of schizophrenia: neurodevelopmental, dopamine dysfunction, viral, and genetic anticipation with unstable DNA. The heuristic value of the epigenetic model of schizophrenia arises from the possibility of integration of a wide variety of empirical data into a new theoretical framework. It can be hypothesized that in addition to pathological effects of DNA structural mutations and environmental factors, inherited and acquired epigenetic defects, or epimutations, may be of etiological importance in schizophrenia. In addition, the epigenetic model may lead to experiments investigating the molecular substrates of genetic-environmental interactions.
Huntington disease: a single-gene degenerative disorder of the striatum (2016)

Huntington disease (HD) is an autosomal dominant, neurodegenerative disorder with a primary etiology of striatal pathology. The Huntingtin gene (HTT) has a unique feature of a DNA trinucleotide (triplet) repeat, with repeat length ranging from 10 to 35 in the normal population. Repeat lengths between 36 and 39 cause HD at reduced penetrance (some will get the disease, others won't) and when expanded to 40 or more repeats (mHTT), causes HD at full penetrance (every person with this length or beyond will definitely develop the disease). The symptoms of HD may be motor, cognitive, and psychiatric, and are consistent with the pathophysiology of frontostriatal circuitry malfunction. Expressed ubiquitously and throughout the entire life cycle (development through adulthood), mHTT causes initial dysfunction and eventual death of a specific cell population within the striatum. Although all areas of the brain are eventually affected, the primary pathology of the disease is regionally specific. As a single-gene disorder, HD has the distinction of having the potential of treatment that is aimed directly at the known pathogenic mechanism by gene silencing, providing hope for neuroprotection and ultimately, prevention.
InstanceCut: From Edges to Instances with MultiCut (2017)

This work addresses the task of instance-aware semantic segmentation. Our key motivation is to design a simple method with a new modelling-paradigm, which therefore has a different trade-off between advantages and disadvantages compared to known approaches. Our approach, we term InstanceCut, represents the problem by two output modalities: (i) an instance-agnostic semantic segmentation and (ii) all instance-boundaries. The former is computed from a standard convolutional neural network for semantic segmentation, and the latter is derived from a new instance-aware edge detection model. To reason globally about the optimal partitioning of an image into instances, we combine these two modalities into a novel MultiCut formulation. We evaluate our approach on the challenging CityScapes dataset. Despite the conceptual simplicity of our approach, we achieve the best result among all published methods, and perform particularly well for rare object classes.
E2F-1 accumulation bypasses a G1 arrest resulting from the inhibition of G1 cyclin-dependent kinase activity. (1995)

Numerous experiments have defined a critical role for the G1 cyclins and associated kinases in allowing a normal progression of cells from a quiescent state, through G1, and into S phase. We now demonstrate that G1 cyclin-dependent kinase activity is critical for the accumulation of E2F activity late in G1. Moreover, E2F-1 overexpression can overcome a G1 arrest caused by the inhibition of G1 cyclin-dependent kinase activity, consistent with E2F activation being an important consequence of the action of G1 cyclins. E2F-1 also overcomes a G1 block caused by gamma irradiation and leads to an apparent complete replication of the cellular genome and entry into mitosis. This E2F-1-mediated induction of S phase and mitosis is not accompanied by the rise in either cyclin D-associated kinase activity or cdk2 activity that is normally observed during the G1 phase of the cell cycle. We conclude that one key function for G1 cyclin-dependent kinase activity is the activation of E2F-1, that the accumulation of E2F activity may be sufficient to allow initiation and completion of S phase, but that additional events, including G1 cyclin kinase activity, are likely necessary for a normal proliferative event.
Recombinant rat CBF-C, the third subunit of CBF/NFY, allows formation of a protein-DNA complex with CBF-A and CBF-B and with yeast HAP2 and HAP3. (1995)

The CCAAT binding factor CBF is a heteromeric transcription factor, which binds to functional CCAAT motifs in many eukaryotic promoters. cDNAs for the A and B subunits of CBF (CBF-A and CBF-B) and for their yeast homologues HAP3 and HAP2 have been previously isolated, but the purified recombinant CBF-A and CBF-B together are unable to bind to CCAAT motifs in DNA. Here we report the isolation of a cDNA coding for rat CBF-C, demonstrate that recombinant CBF-C is required together with CBF-A and CBF-B to form a CBF-DNA complex, and show that CBF-C is present in this protein-DNA complex together with the other two subunits. We further show that CBF-C allows formation of a complex between the purified recombinant yeast HAP2 and HAP3 polypeptides and a CCAAT-containing DNA and is present in this complex, implying the existence of a CBF-C homologue in yeast. We show that CBF-A and CBF-C interact with each other to form a CBF-A-CBF-C complex and that CBF-B does not interact with CBF-A or CBF-C individually but that it associates with the CBF-A-CBF-C complex. Our results indicate that CBF is a unique evolutionarily conserved DNA binding protein.
Designing and Building Oncolytic Viruses (2017)

Oncolytic viruses (OVs) are engineered and/or evolved to propagate selectively in cancerous tissues. They have a dual mechanism of action; direct killing of infected cancer cells cross-primes anticancer immunity to boost the killing of uninfected cancer cells. The goal of the field is to develop OVs that are easily manufactured, efficiently delivered to disseminated sites of cancer growth, undergo rapid intratumoral spread, selectively kill tumor cells, cause no collateral damage and pose no risk of transmission in the population. Here we discuss the many virus engineering strategies that are being pursued to optimize delivery, intratumoral spread and safety of OVs derived from different virus families. With continued progress, OVs have the potential to transform the paradigm of cancer care.
AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α (2007)

Activation of AMP-activated kinase (AMPK) in skeletal muscle increases glucose uptake, fatty acid oxidation, and mitochondrial biogenesis by increasing gene expression in these pathways. However, the transcriptional components that are directly targeted by AMPK are still elusive. The peroxisome-proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) has emerged as a master regulator of mitochondrial biogenesis; furthermore, it has been shown that PGC-1alpha gene expression is induced by exercise and by chemical activation of AMPK in skeletal muscle. Using primary muscle cells and mice deficient in PGC-1alpha, we found that the effects of AMPK on gene expression of glucose transporter 4, mitochondrial genes, and PGC-1alpha itself are almost entirely dependent on the function of PGC-1alpha protein. Furthermore, AMPK phosphorylates PGC-1alpha directly both in vitro and in cells. These direct phosphorylations of the PGC-1alpha protein at threonine-177 and serine-538 are required for the PGC-1alpha-dependent induction of the PGC-1alpha promoter. These data indicate that AMPK phosphorylation of PGC-1alpha initiates many of the important gene regulatory functions of AMPK in skeletal muscle.
Handbook of vibrational spectroscopy (2002)

VOLUME 1: THEORY AND INSTRUMENTATION Introduction to the Theory and Practice of Vibrational Spectroscopy Instrumentation for Mid- and Far-infrared Spectroscopy Instrumentation for Near-infrared Spectroscopy Instrumentation for Raman Spectroscopy Time-resolved Spectroscopy Dichroism and Optical Activity in Vibrational Spectroscopy Surface-enhanced Vibrational Spectroscopy Other Instrumental Approaches for Vibrational Spectroscopy Calibration Procedures and Standards for Vibrational Spectroscopy VOLUME 2: SAMPLING TECHNIQUES Mid- and Near-infrared Transmission Spectroscopy Mid-infrared External Reflection Spectroscopy Mid-infrared Internal Reflection Spectroscopy Diffuse Reflection Spectroscopy Other IR Sampling Techniques Raman Spectroscopy Low Temperature and High Pressure Sampling Techniques Microscopy Depth profiling by Vibrational Spectroscopy Optical Conduits for Vibrational Specroscopy Hyphenated Techniques Atmospheric VOLUME 3: SAMPLE CHARACTERIZATION AND SPECTRAL DATA PROCESSING Spectra-Structure Correlations Group Theoretical and Numerical Approaches to the Calculation of Vibrational Spectra Discrimant Analysis Two-dimensional (2D) Analysis Spectral Enhancement and Band Resolution Techniques Quantitative Analysis Anomalies, Atifacts and Common Errors in Using Vibrational Spectroscopy Techniques Glossary VOLUME 4: APPLICATIONS IN INDUSTRY, MATERIALS AND THE PHYSICAL SCIENCES Analysis and Characterization of Polymers and Rubbers Rheo-optical Measurements of Polymers and Rubbers Materials Science Spectoelectrochemistry Process Vibrational Spectroscopy Atmospheric and Astronomical Vibrational Spectroscopy Industrial Applications of Vibrational Spectroscopy Forensic Applications of Vibrational Spectroscopy Catalysis Other Applications of Vibrational Spectroscopy Vibrational Spectroscopy in Education VOLUME 5: APPLICATIONS IN LIFE, PHARMACEUTICAL AND NATURAL SCIENCES Biomedical Applications Biochemical Applications Pharmaceutical Applications Food Science Agricultural Applications Abbreviations and Acronyms, Glossary, List of Contributors and Subject Index
Amniotic Membrane Wrapping: An Alternative Method to the Splenorrhaphy in the Injured Spleen (1992)

Human amnion, which has been used experimentally and clinically as an ideal bioprosthesis, was used in the present study to wrap the experimentally injured spleens and the technique was compared to splenorrhaphy. Standard splenic injuries were made on 30 male albino rats. 15 of the spleens were repaired by splenorrhaphy and the other 15 were wrapped with sterile human amniotic membrane. Isotope uptakes of the spleens calculated at the 30th postoperative day were similar in both groups (p less than 0.05). But the histopathological examination revealed a better healing in the amnion group with better preservation of the splenic architecture. It was concluded that in heavily injured spleens, amnion wrapping may be an effective alternative to splenorrhaphy.
PRÁTICAS DE AUTOCUIDADO DE HOMENS E MULHERES DO MEIO RURAL (2014)

Objetivo: Conhecer aspectos socioculturais e habitos de vida da populacao rural do Oeste Catarinense e, a partir disso, identificar os determinantes impeditivos para o autocuidado. Metodo: Pesquisa descritiva/exploratoria, realizada com moradores da zona rural de municipios da Regiao, de junho a agosto de 2012, com amostragem aleatoria de 45 homens e 45 mulheres entre 30 e 59 anos de idade. Resultados: Identificou-se o perfil de homens e mulheres que residem e atuam no meio rural, bem como seu estilo de vida. Evidenciou-se que 13,3% dos enfermos nao aderem a tratamento, 75,6% da populacao faz uso de bebidas alcoolicas e 61,1% dos participantes nao realizam atividades fisicas. Os principais fatores impeditivos das praticas de autocuidado foram a sobrecarga do trabalho no campo, a falta de tempo e a falta de conscientizacao. Conclusao: O deficit no autocuidado indica uma carencia de acoes de promocao da saude e prevencao do adoecimento entre a populacao rural.
Comparison of Dual-Rail and TMR Logic Cost Effectiveness and Suitability for FPGAs With Reconfigurable SEU Tolerance (2009)

We compare four circuit methods for single event (SE) mitigation: single string with radiation-hardened flip flops, delay-guarded logic, dual-rail logic, and triple modular redundancy (TMR). Test results of the circuit methods at 180 nm are presented. We then describe a novel reprogrammable FPGA architecture which can be configured based on SE mitigation and performance needs, and we evaluate the candidate SE mitigation methods as to suitability for such architecture.
Antitumor activity and pharmacokinetics in mice of a recombinant immunotoxin containing a disulfide-stabilized Fv fragment. (1994)

Disulfide-stabilized Fvs (dsFv) are recombinant Fv fragments of antibodies in which the inherently unstable VH-VL heterodimer is stabilized by a disulfide bond engineered between structurally conserved framework positions of VH and VL. We have recently described a recombinant immunotoxin, B3(dsFv)-PE38KDEL, that is composed of such a dsFv connected to a truncated form of Pseudomonas exotoxin (PE38KDEL). This disulfide-stabilized immunotoxin is indistinguishable in activity and specificity from its single-chain immunotoxin counterpart (Brinkmann et al., Proc. Natl. Acad. Sci. USA, 90: 7538-7542, 1993). We have now constructed and evaluated the stability, pharmacokinetics, and antitumor effect of a very similar disulfide-stabilized immunotoxin B3(dsFv)-PE38. This immunotoxin is specifically cytotoxic to human cancer cell lines such as A431 that express the B3 antigen on their surface. In addition, the dsFv-immunotoxin is more stable at 37 degrees C in human serum than the corresponding single-chain immunotoxin B3(Fv)-PE38. The survival of the disulfide-stabilized immunotoxin in the circulation of mice was determined by a bioassay on cultured A431 cells after administering the immunotoxin i.v. The half-life in blood was 23 min. To determine the therapeutic effects of the disulfide-stabilized immunotoxin, it was given i.v. to immunodeficient mice bearing s.c. human epidermoid carcinomas. The dsFv-immunotoxin caused complete regression of tumors with no toxic effect on mice. The antitumor effect was similar to that reported for the single-chain Fv-immunotoxin. Our data show that dsFv-immunotoxins retain full in vitro as well as in vivo activity when compared to scFv-immunotoxins. Because dsFv-immunotoxins have full activity, are more stable, and can be produced with significantly improved yields compared to scFv-immunotoxins, the dsFv-immunotoxins may be more useful for therapeutic applications than scFv-immunotoxins.
Changes in the Plasma Membrane of Escherichia coli During Magnesium Starvation (1969)

The effect of Mg(++) starvation on the structure of the Escherichia coli cell membrane was studied with the freeze-etch technique. Special attention was paid to changes within the plane of the membrane, which in normal exponentially growing cells has a netlike arrangement of particles 2 to 6 nm in diameter. During Mg(++) starvation, a paracrystalline particle pattern appeared on the plasma membrane, and large areas devoid of particles were seen. Although these changes are reproducibly associated with Mg(++) starvation of the bacteria, no decrease in the Mg(++) content of the cell envelope per se was detected, even after 24 hr of Mg(++) deprivation. The structural changes caused by Mg(++) deprivation appeared to involve specific and permanent alterations in membrane development. The absence of other nutrients or divalent cations did not induce similar alterations.
Strong Medium and Counterion Effects upon the Redox Potential of the 12-Tungstocobaltate(III/II) Couple. (1991)

The 12-tungstocobaltate(III/II) redox couple, both oxidation states being highly negatively charged (5-/6-), is strongly influenced by the nature of the counterion present. In particular, tetraalkylammonium ions decrease E-degrees[Co(III)/(II)] significantly, relative to that measured in the presence of alkali-metal ions in an organic solvent such as acetonitrile, thus causing large decreases in redox reactivity with respect to oxidation. An increasing proportion of water in the solvent increases E-degrees. The redox properties of the hexachloroiridate(IV)/(III) couple are affected by cations in a similar way.
A Specific Isoform of hnRNP D Interacts with DNA in the LR1 Heterodimer: Canonical RNA Binding Motifs in a Sequence-specific Duplex DNA Binding Protein (1998)

The B cell-specific, sequence-specific duplex DNA-binding protein LR1 is a transcriptional activator and may also function in heavy chain class switch recombination. LR1 is composed of two polypeptides, a 106-kDa subunit that is nucleolin, and a 45-kDa subunit that we now show to be a specific isoform of hnRNP D. hnRNP D and nucleolin both contain canonical RNA binding domains (RBDs also called RRMs) and Arg-Gly-Gly (RGG) motifs. Although these motifs are not commonly associated with sequence-specific recognition of duplex DNA, nonetheless LR1 binds duplex DNA with high affinity (KD = 1.8 nM) and clear sequence specificity. Two RBD-RGG proteins can therefore combine to produce a sequence-specific duplex DNA-binding protein.
HubbleSpaceTelescopeUltraviolet Imaging and High‐Resolution Spectroscopy of Water Photodissociation Products in Comet Hyakutake (C/1996 B2) (1998)

Comet Hyakutake (C/1996 B2) provided a target of opportunity for performing a systematic study of water photodissociation products in which we obtained data from three instruments on the Hubble Space Telescope (HST). The HST Goddard High Resolution Spectrograph (GHRS) was used to measure the line profile of hydrogen Lyα (H Lyα) at six locations around the coma of the comet, ranging from the nucleus to a displacement of 100,000 km, and covering different directions compared with the comet-sun line. GHRS yielded line profiles with a spectral resolution (FWHM ~4 km s^(-1)) that was a factor of 2-3 better than any previous H Lyα or Hα ground-based measurements. The Wide Field Planetary Camera 2 (WFPC2) and the Woods filter were used to obtain H Lyα images of the inner coma. The faint object spectrograph (FOS) was used to determine the OH production rate and monitor its variation throughout the HST observing sequence. The GHRS H Lyα line profiles show the behavior of a line profile that is optically thick in the core for positions near the nucleus (&lt;5000 km) and gradually becoming more optically thin at larger displacements and lower column abundances. A composite H Lyα image constructed from four separate WFPC2 exposures is consistent with the relative fluxes seen in GHRS observations and clearly shows the dayside enhancement of a solar illuminated optically thick coma. These data were analyzed self-consistently to test our understanding of the detailed physics and chemistry of the expanding coma and our ability to obtain accurate water production rates from remote observations of gaseous hydrogen (H) and hydroxyl (OH), the major water dissociation products. Our hybrid kinetic/hydrodynamic model of the coma combined with a spherical radiative transfer calculation is able to account for (1) the velocity distribution of H atoms, (2) the spatial distribution of the H Lyα emission in the inner coma, and (3) the absolute intensities of H and OH emissions, giving a water production rate of (2.6 ± 0.4) × 10^(29) s^(-1) on 1996 April 4.
Considerations in Nerve Repair (2003)

(2003). Considerations in Nerve Repair. Baylor University Medical Center Proceedings: Vol. 16, No. 2, pp. 152-156.