gebhart/patrepeval huggingface dataset:
Circulating tumor cells in breast cancer: Advanced tools for “tailored” therapy? (2006)

Alterations in oncogenes and suppressor genes are critical steps in carcinogenesis and tumor progression in solid and hematological malignancies. The development of therapeutic strategies that interfere with the functional pathways regulated by these genes represents the most successful example of targeted therapy (e.g., imatinib in chronic myelogenous leukemia and trastuzumab in breast cancer) (1, 2). In this issue of PNAS, Meng et al. (3) raise interesting possibilities for exploring circulating tumor cells (CTCs) for personalizing targeted therapy of cancer in the future.
Practical Plant Virology: Protocols and Exercises (1998)

Parts: Virus Inoculation Symptomatology Infectivity assays Infectivity of virus in crude sap Transmission of viruses Maintenance of virus isolates Production of virus-free material from infected plants Virus isolation and purification Physico-chemical properties of virus particles Properties of viral components Serological techniques for detection and identification of viruses and viral products Electron microscope and light microscope serology Detection of viral RNA Diagnosis of a disease and identification of the causal virus(es) The complete table of contents can be found on the Internet. http://www springer.de
Activation of the alternative pathway of complement by twelve different rabbit-mouse chimeric transfectoma IgA isotypes. (1990)

Previous experiments have resulted in the identification and cloning of 13 nonallelic genes encoding the constant region of rabbit IgA H chains. The genes, C alpha 1 to C alpha 13, were each cloned into an expression vector containing the VDJ gene of a dansyl (DNS)-binding murine hybridoma and the constructs were then transfected into SP2/0 cells that were producing murine kappa-L chains from the DNS-binding hybridoma. Of the 13 resulting transfectomas, 12 were shown, by ELISA, to secrete DNS-binding chimeric rabbit-mouse IgA molecules. These transfectoma antibodies, representing 12 different isotypes, are of high affinity and provide a unique source of Ag-specific IgA for comparison of the functions of the multiple IgA isotypes. One such function for antibodies is activation of C by either the classical or alternative pathway. We have used the DNS-binding IgA transfectoma antibodies in C assays based on binding of rabbit C3 to IgA-Ag complexes in an ELISA. The results demonstrated that all 12 IgA isotypes are capable of activating C by the alternative pathway but that none can activate C by the classical pathway. Control experiments demonstrated that activation was hapten dependent and was not caused by endotoxin contamination. These data demonstrate that Ag-specific IgA molecules, unmodified by heat or chemical aggregation, activate C by the alternative pathway but not by the classical pathway.
Peptide Nucleic Acid-Based Array for Detecting and Genotyping Human Papillomaviruses (2009)

We describe a novel array for accurate and reliable genotyping of human papillomavirus (HPV) using peptide nucleic acid (PNA) probes. In order to exploit the superior hybridization properties of PNA with target HPV DNAs, we developed a novel PNA array (PANArray HPV). PANArray HPV enables the detection and genotyping of HPVs using 32 type-specific PNA capture probes for medically important HPVs. All tested HPV types showed highly unique hybridization patterns with type-specific PNA probes. PNA array results showed stable specificities and sensitivities after up to 13 months of storage at room temperature. Also, we demonstrated the superior specificity, sensitivity, and stability of PNA arrays for HPV genotyping. We compared the genotyping results of the PNA array to sequencing with MY09/11 PCR products derived from 72 clinical samples. The results showed excellent agreement between the PNA array and sequencing, except for samples reflecting multiple infections. The results from the PNA array were compared with those of type-specific PCR when discrepant results occurred owing to multiple infections. The results for the PNA array matched those of type-specific PCR in all cases. Newly developed PNA arrays show excellent specificity and sensitivity and long shelf life. Our results suggest that the PNA array represents a reliable alternative to conventional DNA arrays for HPV genotyping, as well as for diagnostics.
Longitudinal Trajectories of Depression and Anxiety in a Prospective Community Study (2003)

These findings have important implications for classification and treatment of affective disorders. The greater stability of comorbid anxiety and depression than either disorder alone illustrates the importance of further investigation of comorbid states compared with noncomorbid states in etiologic and treatment research. The persistence of subthreshold-level depression and anxiety from early to mid adulthood also suggests the importance of characterizing the continuum of expression of depression and anxiety rather than adhering to strict diagnostic thresholds.
Rolled-up nanotechnology for the fabrication of three-dimensional fishnet-type GaAs-metal metamaterials with negative refractive index at near-infrared frequencies (2012)

We propose and demonstrate the fabrication of a three-dimensional fishnet metamaterial by utilizing rolled-up nanotechnology. It consists of 6 alternating layers of silver and (In)GaAs with an array of subwavelength holes “drilled” by focused ion beams. By means of finite-integration technique simulations, we show that the fabricated structure is a single-negative material possessing a negative real part of the refractive index in the near-infrared regime. We show that the fabricated material can be made double negative by slightly changing the size of the holes.
Contrasting Effects of Selection on Sequence Diversity and Linkage Disequilibrium at Two Phytoene Synthase Loci[W] (2003)

We investigated the effects of human selection for yellow endosperm color, representing increased carotenoid content, on two maize genes, the Y1 phytoene synthase and PSY2, a putative second phytoene synthase. Multiple polymorphic sites were identified at Y1 and PSY2 in 75 white and yellow maize inbred lines. Many polymorphic sites showed strong association with the endosperm color phenotype at Y1, but no detectable association was found at PSY2. Nucleotide diversity was equivalent for whites and yellows at PSY2 but was 19-fold less in yellows than in whites at Y1, consistent with the white ancestral state of the gene. The strong sequence haplotype conservation within yellows at Y1 and a significant, negative Tajima's D both verified positive selection for yellow endosperm. We propose that two independent gain-of-function events associated with insertions into the promoter of the Y1 gene and upregulation of expression in endosperm have been incorporated into yellow maize.
Thalidomide: The Tragedy of Birth Defects and the Effective Treatment of Disease (2011)

Thalidomide was a widely used drug in the late 1950s and early 1960s for the treatment of nausea in pregnant women. It became apparent in the 1960s that thalidomide treatment resulted in severe birth defects in thousands of children. Though the use of thalidomide was banned in most countries at that time, thalidomide proved to be a useful treatment for leprosy and later, multiple myeloma. In rural areas of the world that lack extensive medical surveillance initiatives, thalidomide treatment of pregnant women with leprosy has continued to cause malformations. Research on thalidomide mechanisms of action is leading to a better understanding of molecular targets. With an improved understanding of these molecular targets, safer drugs may be designed. The thalidomide tragedy marked a turning point in toxicity testing, as it prompted United States and international regulatory agencies to develop systematic toxicity testing protocols; the use of thalidomide as a tool in developmental biology led to important discoveries in the biochemical pathways of limb development. In celebration of the Society of Toxicology's 50th Anniversary, which coincides with the 50th anniversary of the withdrawal of thalidomide from the market, it is appropriate to revisit the lessons learned from the thalidomide tragedy of the 1960s.
Clinical relevance of persistently elevated circulating cytokines (tumor necrosis factor α and interleukin‐6) in the long‐term followup of patients with giant cell arteritis (2010)

Circulating TNFalpha and IL-6 may persist elevated in GCA patients after long-term followup and remain higher in patients who have experienced more relapsing disease. However, in this patient cohort, elevated circulating cytokines were not associated with increased frequency of GCA complications, vascular events, or treatment-related side effects.
Perceived visual motion descriptors from MPEG-2 for content-based HDTV annotation and retrieval (1999)

Efficient content-based search and retrieval of video databases has become an important industrial and consumer application due to rapid proliferation of compressed digital video data on the Internet and corporate Intranets, and due to the launch of high definition television (HDTV) broadcasts in 1998. We have developed the first HDTV video content management system that automatically analyzes motion occurring in MPEG-2 encoded videos within the compressed domain itself. Our system produces descriptors characterizing the global motion in videos for content retrieval and repurposing applications in a digital television studio. These motion-direction and magnitude based video labels can be directly, incorporated as annotation indexes into a database for querying, or used to construct higher level event descriptions of videos. Results from our ongoing experiments with tens of thousands of frames obtained from several MPEG-1,2 video streams of various genres demonstrate the good performance of our annotation system in terms of motion identification accuracy and computational efficiency.
Potent Dibasic GPIIb/IIIa Antagonists with Reduced Prolongation of Bleeding Time:  Synthesis and Pharmacological Evaluation of 2-Oxopiperazine Derivatives (2001)

A series of 2-oxopiperazine derivatives, possessing basic moieties at the 3- and the 4-positions, were synthesized and evaluated for their abilities to inhibit platelet aggregation and for their effects on bleeding time. Among the compounds, 2-[(3S)-4-[2-[(4-guanidinobenzoyl)amino]acetyl]-3-[3-[(4-guanidinobenzoyl)amino]propyl]-2-oxopiperazinyl]acetic acid (12c) showed a potent inhibitory effect on platelet aggregation and good dissociation between the efficacy and the bleeding side effect. Intravenous infusion of compound 12c at 1.6 microg/mL/min completely prevented arterial thrombus formation induced by endothelial injury in guinea pigs. The dose of 12c that prolonged the bleeding time to three times the control value was 5.8 microg/mL/min. These results suggest that compound 12c might be useful in the clinical treatment of thrombotic diseases, and we selected 12c (TAK-024) as a candidate for the clinical trials.
Physical modifying effects and their influence on the crystallization of casting alloys (2015)

Basic theoretical propositions on physical modifying effects (vibration, ultrasonic, electromagnetic agitation, and thermal-temporal processing) on the crystallization of casting alloys are generalized. Mathematical calculations and experimental investigations have revealed that the crystallization and structure formation of casting alloys could be largely determined by the treatment technology using the physical effects during melting and casting. The physical effects on a crystallizing melt cause its strong turbulization and agitation, thereby decreasing the temperature and concentration gradients in the melt, eliminating overheating the liquid phase with respect to the solidus temperature, and breaking off dendrites (which are good crystallization seeds for overall melt volume). The evaluation of the dendrite growth during crystallization showed that splitting the dendrite grains is opposed to their coarsening under physical effects. The physical effects result in bulk crystallization with equiaxed grains without the formation of the columnar structure. The physical modifying effects promote the improvement of the quality of acquired alloys and casts made of them under the conditions of their rational application.
Comparison of effects of the tyrosine kinase inhibitors AG957, AG490, and STI571 on BCR-ABL–expressing cells, demonstrating synergy between AG490 and STI571 (2001)

STI571 (formerly CGP57148) and AG957 are small molecule inhibitors of the protein tyrosine kinase (PTK) p145(abl) and its oncogenic derivative p210(bcr-abl). AG490 is an inhibitor of the PTK Janus kinase 2 (JAK2). No direct comparison of these inhibitors has previously been reported, so this study compared their effects on factor-dependent FDC-P1, 32D, and MO7e cells and their p210(bcr-abl)-expressing factor-independent derivatives. STI571 was a more potent inhibitor of (3)H-thymidine incorporation in p210(bcr-abl)-expressing cells than was AG957, and it showed superior discrimination between inhibitory effects on parental cell lines and effects on their p210(bcr-abl)-expressing derivatives. Assays performed with and without growth factor demonstrated that STI571 but not AG957 reversed the p210(bcr-abl)-driven factor independence of cell lines. p210(bcr-abl)-expressing cells were less sensitive to AG490 than to AG957 or STI571. However, for p210(bcr-abl)-expressing clones from all 3 cell lines, synergistic inhibition was demonstrated between STI571 and concentrations of AG490 with no independent inhibitory effect. Inhibition of nucleic acid synthesis with AG957 treatment was associated with reduced cell numbers, reduced viability, and small pyknotic apoptotic cells. At concentrations of STI571 that reversed the p210(bcr-abl) factor-independent phenotype, STI571 treatment and growth factor deprivation together were sufficient to induce apoptosis. This study concludes that, for the cell lines studied, (1) STI571 is a more potent and more selective inhibitor of a p210(bcr-abl)-dependent phenotype than AG957; (2) AG490 synergizes with STI571 to enhance its inhibitory effect on p210(bcr-abl)-driven proliferation; and (3) the combination of p210(bcr-abl)-tyrosine kinase inhibition and growth factor signal withdrawal can be sufficient to induce apoptotic death of transformed cells. (Blood. 2001;97:2008-2015)
Surface and thermomechanical characterization of polyurethane networks based on poly(dimethylsiloxane) and hyperbranched polyester (2013)

Two series of polyurethane (PU) networks based on Boltorn hyperbranched polyester (HBP) and hydroxyethoxy propyl terminated poly(dimethylsiloxane) (EO-PDMS) or hydroxy propyl terminated poly(dimethylsiloxane) (HP-PDMS), were synthesized. The effect of the type of soft PDMS segment on the properties of PUs was investigated by Fourier transform infrared spectroscopy (FTIR), contact angle measurements, surface free energy determination, X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), atomic force microscopy (AFM), dynamic mechanical thermal analysis (DMTA) and differential scanning calorimetry (DSC). The surface characterization of PUs showed existence of slightly amphiphilic character and it revealed that PUs based on HP-PDMS have lower surface free energy, more hydrophobic surface and better waterproof performances than PUs based on EO-PDMS. PUs based on HP-PDMS had higher crosslinking density than PUs based on EO-PDMS. DSC and DMTA results revealed that these newlysynthesized PUs exhibit the glass transition temperatures of the soft and hard segments. DMTA, SEM and AFM results confirmed existence of microphase separated morphology. The results obtained in this work indicate that PU networks based on HBP and PDMS have improved surface and thermomechanical properties.
Recent advances in optic nerve glioma with a focus on the young patient. (2003)

Visual pathway low-grade astrocytomas of childhood are the subject of diverse research into diagnostic aetiological and treatment aspects aimed at tailoring diagnostic and treatment procedures more precisely to the needs of the young patient for this tumour type.
Long-term Safety and Efficacy of a New Botulinum Toxin Type A in Treating Glabellar Lines (2009)

To evaluate the long-term safety of repeated administrations of a new botulinum toxin type A (Reloxin; Medicis Pharmaceutical Corp, Scottsdale, Arizona) in the treatment of moderate to severe glabellar lines. Open-label assessment of 1200 patients receiving as many as 5 treatments of Reloxin over a 13-month period. The product was diluted in 2.5-mL sterile physiologic saline solution, 0.9%, without preservative to a concentration of 50 U of Reloxin per 0.25 mL of solution. Investigators injected 0.05 mL of the solution (10 U each) into each of 5 injection sites in the glabellar area on day 0 of each treatment cycle. There was a minimum 85-day gap between treatments. Postinjection clinical evaluation was performed on days 14 and 30 and monthly thereafter until retreatment, study completion, or early termination. The patients were telephoned on day 7 to check for adverse events (AEs) and concomitant medications, and patient diaries were used to document the onset of treatment effect. The majority (72%) of treatment-emergent AEs were considered unlikely or not related to study treatment. Probably or possibly related treatment-emergent AEs occurred in 36% of patients. The most frequently occurring related AEs were injection site disorders (18%), nervous system disorders (14% and 12% headache), and eye disorders (9%). Related AEs around the injection site or eyes were usually reported by day 7 and then resolved. Reported ptosis does not differentiate between brow ptosis and eyelid ptosis. A total of 45 patients had a total of 55 instances of ptosis across all cycles, with most episodes lasting less than 3 weeks. The rates of ptosis decreased during successive cycles from 2.4% in cycle 1 to 0.6% in cycle 5. The proportion of patients reporting an onset of response by day 7 ranged from 93% to 95%. By investigator assessment, the response rate (patients reporting none or mild glabellar line severity scale scores on day 30) ranged from 80% to 91% during cycles 1 to 5. There was no evidence of cumulative AEs or tachyphylaxis with multiple Reloxin treatments over a period of 13 months. The treatments were well tolerated. The rates of ptosis decreased over successive cycles, and the proportion of responders by day 7 ranged from 93% to 95%.
Direct patterning of nanometer-scale silicide structures on silicon by ion-beam implantation through a thin barrier layer (2001)

CoSi 2 structures were formed by focused ion-beam implantation. Patterned silicide lines with dimensions down to 150 nm were produced on (100) silicon. The process involved the ion implantation of 200 keV As++ through a cobalt (34 nm)/oxide (∼2 nm) thin film structure. The thin oxide at the Si/Co interface acted as a selective reaction barrier. Ion-beam mixing disrupted the oxide layer to allow silicidation to proceed during subsequent rapid thermal anneal treatments. Reactions were inhibited in nonimplanted areas. A threshold dose of 3×1015 cm−2 was required for process initiation. Electrical measurements resulted in resistivities ranging from 15 to 30 μΩ cm.
Np95 Is a Histone-Binding Protein Endowed with Ubiquitin Ligase Activity (2004)

Np95 is an important determinant in cell cycle progression. Its expression is tightly regulated and becomes detectable shortly before the entry of cells into S phase. Accordingly, Np95 is absolutely required for the G1/S transition. Its continued expression throughout the S/G2/M phases further suggests additional roles. Indeed, Np95 has been implicated in DNA damage response. Here, we show that Np95 is tightly bound to chromatin in vivo and that it binds to histones in vivo and in vitro. The binding to histones is direct and shows a remarkable preference for histone H3 and its N-terminal tail. A novel protein domain, the SRA-YDG domain, contained in Np95 is indispensable both for the interaction with histones and for chromatin binding in vivo. Np95 contains a RING finger. We show that this domain confers E3 ubiquitin ligase activity on Np95, which is specific for core histones, in vitro. Finally, Np95 shows specific E3 activity for histone H3 when the endogenous core octamer, coimmunoprecipitating with Np95, is used as a substrate. Histone ubiquitination is an important determinant in the regulation of chromatin structure and gene transcription. Thus, the demonstration that Np95 is a chromatin-associated ubiquitin ligase suggests possible molecular mechanisms for its action as a cell cycle regulator.
Bio-inspired controlled release through compression–relaxation cycles of microcapsules (2015)

The aim of microencapsulation is to achieve controllable and sustainable release at the desired site. Despite the many methods developed in recent years, there is still a need to advance the strategies for higher controllability and scalability. Taking inspiration from the heart, which pumps blood by continual contraction of muscles, we demonstrate a novel releasing method, in which the core release is controlled by the compression–relaxation cycles of microcapsules upon the application of a magnetic field. This idea is realized by embedding Fe3O4 particles into a polymer shell. When the magnetic field is applied, the Fe3O4 particles align along the field direction and stretch the shell, resulting in compression of the microcapsules and release of the core contents; the shape is restored after the field is removed. We demonstrated various release patterns by altering the strength of the magnetic field and the compression frequency. This release method provides repeated and pulsatile delivery, enhanced spreading distance and ejection speed, and is site specific and proactive, providing a new option for controlled release applications. A new drug-release method based on constricting magnetic microcapsules by applying a magnetic field has been developed by a team in China. The researchers, who are from the Chinese Academy of Sciences in Beijing, were inspired by the action of heart muscles pushing blood out from the heart. In a proof-of-principle study, they made the magnetic microcapsules by embedding Fe3O4 microparticles in polymer shells. On applying a magnetic field, the Fe3O4 particles aligned parallel to the field, causing the shells to elongate, thereby compressing the microcapsules so that they released their contents. When the field was removed, the microcapsules returned to their original shape. This method is highly controllable and permits repeated, pulsed delivery. Furthermore, it is site specific and provides greater delivery distance and speed than conventional drug delivery methods. A novel release mechanism of microcapsules is demonstrated, where the rate of core release can be solely controlled by magnetic field-induced deformation of microcapsules. Composite microcapsules are prepared with magnetic particles embedded in the polymer wall. It shows that the release rate is highly dependent on the strengths of the magnetic field and deformation frequency of the microcapsules.