gebhart/patrepeval huggingface dataset:
<title>High-sensitivity immunoassay using a novel upconverting phosphor reporter</title> (1997)

A new class of reporter label, consisting of rare earth elements embedded in a crystalline particle, has been developed for in vitro diagnostic applications. These unique labels upconvert low energy (IR) radiation to high energy light by a multiphoton absorption process and subsequent phosphorescence emission. As a result, upconverting phosphors can be visualized with no biological background or autofluorescence signal. In addition, phosphors have narrow absorption and emission bands, making them ideal for simultaneous multianalyte test. The crystalline nature of the phosphors makes them insensitive to environmental conditions, with essentially infinite shelf life and no photobleaching at the irradiances used for excitation. We have covalently coupled (Y<SUB>0.86</SUB>Yb<SUB>0.08</SUB>Er<SUB>0.06</SUB>)<SUB>6</SUB>O<SUB>2</SUB>S phosphor labels to antibody probes to create a reporter reagent that can be excited by 980 nm radiation from a diode laser and detected by a modified spectrofluorimeter. Target analyte sensitivities of approximately 10 ng/mL to Staphylococcal enterotoxin B have been demonstrated using a sandwich assay in a magnetic bead or capillary wick formats in a non-optimized assay system. These results are directly applicable to the development of assays that can be performed on microfabricated biochips or in microflow channels.
ChemInform Abstract: PROPERTIES OF BIS(TRIFLUOROACETOXY)BORANE AS A REDUCING AGENT OF ORGANIC COMPOUNDS (1981)

Abstract Bis‐trifluoracetoxy‐boran wird in Form des Tetrahydrofuran‐Adduktes (II) als Reduktionsmittel eingesetzt, und zunächst werden (I), (IV), (VI)‐(VIII) und (XI) reduziert.
On the evolution of clusters of near-duplicate Web pages (2004)

We expand on a 1997 study of the amount and distribution of near-duplicate pages on the World Wide Web. We downloaded a set of 150 million Web pages on a weekly basis over the span of 11 weeks. We then determined which of these pages are near-duplicates of one another, and tracked how clusters of near-duplicate documents evolved over time. We found that 29.2% of all Web pages are very similar to other pages, and that 22.2% are virtually identical to other pages. We also found that clusters of near-duplicate documents are fairly stable: Two documents that are near-duplicates of one another are very likely to still be near-duplicates 10 weeks later. This result is of significant relevance to search engines: Web crawlers can be fairly confident that two pages that have been found to be near-duplicates of one another will continue to be so for the foreseeable future, and may thus decide to recrawl only one version of that page, or at least to lower the download priority of the other versions, thereby freeing up crawling resources that can be brought to bear more productively somewhere else.
Physics of biofilms: the initial stages of biofilm formation and dynamics (2014)

One of the physiological responses of bacteria to external stress is to assemble into a biofilm. The formation of a biofilm greatly increases a bacterial population's resistance to a hostile environment by shielding cells, for example, from antibiotics. In this paper, we describe the conditions necessary for the emergence of biofilms in natural environments and relate them to the emergence of biofilm formation inside microfluidic devices. We show that competing species of Escherichia coli bacteria form biofilms to spatially segregate themselves in response to starvation stress, and use in situ methods to characterize the physical properties of the biofilms. Finally, we develop a microfluidic platform to study the inter-species interactions and show how biofilm-mediated genetic interactions can improve a species’ resistance to external stress.
Phase propagation in ultrasonic backscatter monitoring of high intensity focused ultrasound therapy. (2011)

Phase propagation using the Rytov method has recently been proposed as a means for modeling the time-of-flight changes induced by thermal therapy [Speyer et al., J. Acoust. Am. 127]. These results are extended to measurements from a linear array, under which the general problem of imaging material changes is cast. The linear array offers several design components, which can be exploited for therapy monitoring, including the apodization and probing frequency. Phase propagation models are shown to be consistent with many aspects of conventional modeling, linearizing material changes around the same operating points as have been proposed by other researchers, and providing time-of-flight changes linearly related to the temperature distribution under these conditions. Beyond expanding on model properties, experimental evidence is presented, which indicates that phase propagation modeling is significantly more consistent with backscattered ultrasound data than conventional ray approaches. [Work supported by NIH Grant No. 5R01CA109557.]
Some Reactions of Pyrido[4,3-b]indole (g-Carboline) (1981)

N-oridation and N -m i n a t i o n of pyridd4.3-blindole( Ic n r b o t i n e l mtd reactions of the 2-olide w i t h phosphorus oqchZoride, a c e t i c anhydride, phenyZ i s m y a t e mtd cymwgen bmmide were described.Recently 3-amino-1-methyl-(la) and 3-amino-1.4-dimethylpyrido[4,3-blindole( l & ) were i s o -1 l a t e d as very potent mutagens i n a pyrolysate o f L-tryptophan and proved t o be carcinogenic.2 3 These compounds were synthesized and b i o l o g i c a l studies are i n progress.4'5On the other hand, chemical study on pyrido[4,3-blindole (2; y-carboline) i s very poor compared t o t h a t on pyrido-[3,4-blindole (2; 0-carboline).Only the synthesis o f the s k e l e t a l compound has been reported. 6This paper reports on some reactions o f y-carboline (2) and synthesis of amino-y-carbolines i n r e l a t i o n t o the potent mutagens.
Frontispiece: Enzymatic Late‐Stage Oxidation of Lead Compounds with Solubilizing Biomimetic Docking/Protecting groups (2018)

Combining biocatalytic oxidation with protective-group chemistry enables one to modulate the site of oxidation. Lead compounds protected with different solubilizing biomimetic docking/protecting groups yield different hydroxylated derivatives with the same P450BM3-mutant. Additional hydroxylation products are obtained when the P450BM3-mutant is also varied. Derivatives of this type are difficult to obtain otherwise. Additionally, molecular-dynamic simulations help to rationalize the observed oxidation patterns. For more information, see the Full Paper by U. E. W. Lange et al. on page 17936 ff.
Natural product (−)‐gossypol inhibits colon cancer cell growth by targeting RNA‐binding protein Musashi‐1 (2015)

Musashi-1 (MSI1) is an RNA-binding protein that acts as a translation activator or repressor of target mRNAs. The best-characterized MSI1 target is Numb mRNA, whose encoded protein negatively regulates Notch signaling. Additional MSI1 targets include the mRNAs for the tumor suppressor protein APC that regulates Wnt signaling and the cyclin-dependent kinase inhibitor P21(WAF-1). We hypothesized that increased expression of NUMB, P21 and APC, through inhibition of MSI1 RNA-binding activity might be an effective way to simultaneously downregulate Wnt and Notch signaling, thus blocking the growth of a broad range of cancer cells. We used a fluorescence polarization assay to screen for small molecules that disrupt the binding of MSI1 to its consensus RNA binding site. One of the top hits was (-)-gossypol (Ki = 476 ± 273 nM), a natural product from cottonseed, known to have potent anti-tumor activity and which has recently completed Phase IIb clinical trials for prostate cancer. Surface plasmon resonance and nuclear magnetic resonance studies demonstrate a direct interaction of (-)-gossypol with the RNA binding pocket of MSI1. We further showed that (-)-gossypol reduces Notch/Wnt signaling in several colon cancer cell lines having high levels of MSI1, with reduced SURVIVIN expression and increased apoptosis/autophagy. Finally, we showed that orally administered (-)-gossypol inhibits colon cancer growth in a mouse xenograft model. Our study identifies (-)-gossypol as a potential small molecule inhibitor of MSI1-RNA interaction, and suggests that inhibition of MSI1's RNA binding activity may be an effective anti-cancer strategy.
Cyclin‐dependent protein kinase 5 (Cdk5) and the regulation of neurofilament metabolism (2001)

Cyclin-dependent kinase 5 (Cdk5), a complex of Cdk5 and its activator p35 (Cdk5/p35), phosphorylates diverse substrates which have multifunctional roles in the nervous system. During development, it participates in neuronal differentiation, migration, axon outgrowth and synaptogenesis. Cdk5, acting together with other kinases, phosphorylates numerous KSPXK consensus motifs in diverse cytoskeletal protein target molecules, including neurofilaments, and microtubule associated proteins, tau and MAPs. Phosphorylation regulates the dynamic interactions of cytoskeletal proteins with one another during all aspects of neurogenesis and axon radial growth. In this review we shall focus on Cdk5 and its regulation as it modulates neurofilament metabolism in axon outgrowth, cytoskeletal stabilization and radial growth. We suggest that Cdk5/p35 forms compartmentalized macromolecular complexes of cytoskeletal substrates, other neuronal kinases, phosphatases and activators ('phosphorylation machines') which facilitate the dynamic molecular interactions that underlie these processes.
On-line assessment of HIFU beams and lesion monitoring using dual-transducer modes (2004)

A dual-transducer system was used to test concepts for on-line guidance and lesion monitoring during ultrasound therapy. The system used a spherical-cap therapy transducer with a central, A-mode transducer. Three operational modes were successfully tested in in-vitro liver specimens. Mode 1 senses in-situ therapy-beam harmonics that affect absorption and heating. The therapy transducer emits a 2 /spl mu/s pulse at the same amplitude used in therapy; echoes from this pulse are received with the A-mode transducer and digitally filtered to produce A-scans at the therapy frequency and its harmonics. Mode 2 detects lesions by virtue of their increased stiffness. A 1-ms therapy-transducer pulse produces radiation force and internal tissue motion that is tracked by cross-correlating sequential A-scans. The procedure is repeated after therapy to detect motion changes due to formed lesions. Mode 3 uses the A-mode transducer (pulse-echo) to sense lesions with increased attenuation and scattering using sliding-window spectrum analysis.
Design of thin InGaAsN(Sb) n - i - p junctions for use in four-junction concentrating photovoltaic devices (2017)

Four-junction solar cells for space and terrestrial applications require a junction with a band gap of ∼1 eV for optimal performance. InGaAsN or InGaAsN(Sb) dilute nitride junctions have been demonstrated for this purpose, but in achieving the 14 mA/cm2 short-circuit current needed to match typical GaInP and GaAs junctions, the open-circuit voltage (VOC) and fill factor of these junctions are compromised. In multijunction devices incorporating materials with short diffusion lengths, we study the use of thin junctions to minimize sensitivity to varying material quality and ensure adequate transmission into lower junctions. An n-i-p device with 0.65-μm absorber thickness has sufficient short-circuit current, however, it relies less heavily on field-aided collection than a device with a 1-μm absorber. Our standard cell fabrication process, which includes a rapid thermal anneal of the contacts, yields a significant improvement in diffusion length and device performance. By optimizing a four-junction cell around a smaller 1-sun short-circuit current of 12.5 mA/cm2, we produced an InGaAsN(Sb) junction with open-circuit voltage of 0.44 V at 1000 suns (1 sun=100 mW/cm2), diode ideality factor of 1.4, and sufficient light transmission to allow >12.5 mA/cm2 in all four subcells.
DOA Estimation of Two Targets with Deep Learning (2018)

Direction of arrival (DOA) estimation of radio waves is demanded in many situations. In addition to MUSIC and ESPRIT, which are well-known traditional algorithms, compressed sensing has been recently applied to DOA estimation. If a large computational load as seen in some of compressed sensing algorithms is acceptable, it may be possible to apply deep learning to DOA estimation. In this paper, we propose estimating DOAs using deep learning and discuss training data preparation and designing for a specific scenario. The simulation results show reasonably-high estimation accuracy, performance dependency on training data preparation, and effectivity of specialized deep neural network.
Weekly ixabepilone with or without concurrent bevacizumab in the treatment of recurrent endometrial cancer. (2012)

e15526 Background: Ixabepilone for endometrial cancer has only been evaluated in phase II studies administered at 30-40 mg/m 2 q21 days (GOG 129P, GOG 86P). The objective of this study is to describe the institutional experience using a weekly dosing strategy of ixabepilone ± bevacizumab in the treatment of paclitaxel/platinum-resistant recurrent endometrial cancer. Methods: Patients who received weekly ixabepilone (16-20 mg/m 2 on days 1, 8, 15 of a 28-day cycle) ± bevacizumab (10 mg/kg on days 1, 15 of a 28-day cycle) off-protocol were identified retrospectively. Results: Thirteen patients were included. Demographic/disease characteristics are provided in Table 1. Median time to first recurrence was 15.9 months (IQR: 9.5-21.66). Patients received a mean of 4.8 ± 1.9 cycles of ixabepilone; treatment is ongoing in 4 patients. A total of 46% of patients demonstrated either a partial response (PR, 8%) or disease stabilization (SD, 38%). PR/SD was associated with a mean decline in CA-125 of 56%. Approximately 50% of patients received concurrent bevacizumab. Of patients who did not receive concurrent bevacizumab, 83% experienced progression and 17% demonstrated SD. Median survival after ixabepilone initiation was 12.7 and 6.9 months in patients treated with and without concurrent bevacizumab, respectively (HR 0.42 [0.09-1.98]). Grade 1/2 hematologic (thrombocytopenia, 15.4%) and gastrointestinal toxicities (emesis/constipation, 7.7%) were observed infrequently. Median overall survival of this cohort was 2.88 years. Conclusions: Ixabepilone shows encouraging activity and promising durability in patients with heavily pre-treated paclitaxel/platinum-resistant recurrent endometrial cancer. Weekly dosing at 16-20mg/m 2 on days 1, 8, and 15 ± bevacizumab is well-tolerated. Additional investigation of this regimen and long-term follow-up is warranted. [Table: see text]
Wide scan, integrated printed circuit board, fragmented aperture array antennas (2011)

Over the last decade, fragmented aperture antennas have been developed to support bandwidths up to 33:1 and higher. Largely, these extreme bandwidth apertures have been developed to support receive applications. In this paper, we present a new design approach to increasing the scan volume to beyond 60 deg, a simplified printed circuit board fabrication approach, and a sample whole x-band (8-12 GHz) array antenna that demonstrates the new design and fabrication approach.
Pseudomonas exotoxin A mutants. Replacement of surface-exposed residues in domain III with cysteine residues that can be modified with polyethylene glycol in a site-specific manner. (1994)

Pseudomonas exotoxin A (PE) is composed of three structural and functional domains.Domain Ia is respon- sible for cell recognition, domain I1 for translocation of PE across the cell membrane, and domain I11 for ADPribosylation of elongation factor 2. To investigate the role of the amino acids exposed on the surface of domain 111, we replaced 15 of these, generating 29 different mutants at positions 412,416,418,490,513,516,522,551,576, 590, 599, 604, 606, 607 and 608.All but one mutant retained substantial ADP-ribosylation and cytotoxic activities.Modification of proteins with monomethoxypolyethylene glycol (mPEG) prolongs their circulation in the blood stream and reduces their immunogenicity.Unlike PEGylated enzymes acting on small molecule substrates, PEGylated toxins may lose those functions that are based on macromolecular interactions.Therefore, we selectively PEGylated mutant PES at positions 490,513,516,522,604, and 606.Most PES modified by a 5-kDa mPEG via a disulfide or a thioether bond retained high cytotoxic activity.However, when a 20-kDa mPEG was used there was a decrease in cytotoxic activity with the disulfide-bonded molecules being more active.Positions 522 and 604 are good sites for PEGylation, but 490 is not.W e also found that PEGylation of PE 522C prolonged its in vivo circulation time in mice.
Estimation and equalization of time-selective fading channels (2003)

Time-selective fading effects can occur in communication systems due to channel variations, carrier frequency offset, and oscillator's phase noise. In this paper, we model the multiplicative channel fading effect as an autoregressive process and the objective is to recover the original transmitted symbols. Filterbanks are used here to precode the transmitted symbols and second-order statistics of the output data are computed which in turn, yield the correlation information of the time-varying channel. Next, we employ the Kalman filter to track channel variations and recover the transmitted symbols in a block-by-block fashion. For the Rayleigh fading case, we also take advantage of the additional information provided by pilot symbol assisted modulation (PSAM) to resolve channel ambiguities. Computer simulations are provided to illustrate the concepts.
NsaRS is a cell-envelope-stress-sensing two-component system of Staphylococcus aureus (2011)

Staphylococcus aureus possesses 16 two-component systems (TCSs), two of which (GraRS and NsaRS) belong to the intramembrane-sensing histidine kinase (IM-HK) family, which is conserved within the firmicutes. NsaRS has recently been documented as being important for nisin resistance in S. aureus. In this study, we present a characterization of NsaRS and reveal that, as with other IM-HK TCSs, it responds to disruptions in the cell envelope. Analysis using a lacZ reporter-gene fusion demonstrated that nsaRS expression is upregulated by a variety of cell-envelope-damaging antibiotics, including phosphomycin, ampicillin, nisin, gramicidin, carbonyl cyanide m-chlorophenylhydrazone and penicillin G. Additionally, we reveal that NsaRS regulates a downstream transporter NsaAB during nisin-induced stress. NsaS mutants also display a 200-fold decreased ability to develop resistance to the cell-wall-targeting antibiotic bacitracin. Microarray analysis reveals that the transcription of 245 genes is altered in an nsaS mutant, with the vast majority being downregulated. Included within this list are genes involved in transport, drug resistance, cell envelope synthesis, transcriptional regulation, amino acid metabolism and virulence. Using inductively coupled plasma-MS we observed a decrease in intracellular divalent metal ions in an nsaS mutant when grown under low abundance conditions. Characterization of cells using electron microscopy reveals that nsaS mutants have alterations in cell envelope structure. Finally, a variety of virulence-related phenotypes are impaired in nsaS mutants, including biofilm formation, resistance to killing by human macrophages and survival in whole human blood. Thus, NsaRS is important in sensing cell damage in S. aureus and functions to reprogram gene expression to modify cell envelope architecture, facilitating adaptation and survival.
Critical currents in sputtered copper molybdenum sulphide (1977)

Critical currents in a sputtered Chevrel-phase copper molybdenum sulphide have been measured at 4.2 K as a function of applied magnetic field. Self-field critical-current values up to 109 A/m2 were found, decreasing to 108 A/m2 at 3 T. Graphs of pinning forces versus field were found to be independent of field direction, and the pinning mechanism is sample independent. Critical-current densities for sputtered lead molybdenum sulphide are estimated to be ≳108 A/m2 at 26 T based on a scaling law for pinning.
A phase I, open-label, dose-escalation and cohort expansion study evaluating the safety and immune response to autologous dendritic cells transduced with AdGMCA9 in patients with metastatic renal cell carcinoma. (2018)

653 Background: We developed a fusion gene construct, GM-CSF + CAIX, transduced by a replication deficient adenovirus into autologous dendritic cells (DC) that are injected in patients with metastatic RCC (mRCC) in this phase 1 study targeting CAIX overexpressed on RCC tumors. Methods: A recombinant adenovirus encoding the GMCSF-CAIX fusion gene (AdGMCAIX) manufactured per GMP in collaboration with the NCI Rapid Access to Intervention Development (RAID) program. The final product was produced using DCs produced ex-vivo from patients’ peripheral blood mononuclear cells (PBMC), by culturing with GM-CSF &amp; IL-4, then engineered with AdGMCAIX prior to intradermal injection. The injected transduced DCs were expected to stimulate an antigen specific immune response against CAIX expressing RCC. Three dose escalation cohorts (5, 15, and 50 X 106 cells/administration) were injected based on 3+3 design. DC-AdGMCAIX was given intradermally q2wkX3 doses. The primary aim is safety. Secondary aims are to evaluate immune responses &amp; antitumor effects per RECIST 1.1. Eligibility criteria included patients with clear cell mRCC with ECOG 0-1, measurable disease, and adequate organ function. Results: Fifteen patients with clear cell mRCC were enrolled. Nine patients received all 3 planned vaccine doses, comprising DC expressing CAIX, CD11c and other relevant markers. No serious adverse events (SAEs) were seen. Grade 1/2 AEs include fatigue (3/1), leukopenia (1/1) and flu-like symptoms (0/1). Of the 9 patients who received treatment, 1 expired of progressive disease (PD), 2 patients were lost to follow-up and 6 patients are alive. Of the 6 patients, 5 have PD and are currently receiving standard-of-care therapies, and 1 has completed treatment with stable disease at 6 mon follow up and is being evaluated for retreatment. Conclusions: These early data show that autologous DC transduced by Ad-GMCAIX vector can be safely given to mRCC patients without any SAEs noted at the doses tested. These data support further development of Ad-GMCAIX vaccine strategies, either alone, or in combination with approved therapies. Clinical trial information: NCT01826877.
Impact of upfront cellular enrichment by laser capture microdissection on protein and phosphoprotein drug target signaling activation measurements in human lung cancer: Implications for personalized medicine (2015)

These results indicate that LCM driven upfront cellular enrichment is necessary to accurately determine the expression/activation levels of predictive protein signaling markers although results should be evaluated in larger clinical settings. Upfront cellular enrichment of the target cell appears to be an important part of the workflow needed for the accurate quantification of predictive protein signaling biomarkers. Larger independent studies are warranted.