gebhart/patrepeval huggingface dataset:
Collision tumors revealed by prospectively assessing subtype-defining molecular alterations in 904 individual prostate cancer foci (2022)

BACKGROUNDProstate cancer is multifocal with distinct molecular subtypes. The utility of genomic subtyping has been challenged due to inter- and intrafocal heterogeneity. We sought to characterize the subtype-defining molecular alterations of primary prostate cancer across all tumor foci within radical prostatectomy (RP) specimens and determine the prevalence of collision tumors.METHODSFrom the Early Detection Research Network cohort, we identified 333 prospectively collected RPs from 2010 to 2014 and assessed ETS-related gene (ERG), serine peptidase inhibitor Kazal type 1 (SPINK1), phosphatase and tensin homolog (PTEN), and speckle type BTB/POZ protein (SPOP) molecular status. We utilized dual ERG/SPINK1 immunohistochemistry and fluorescence in situ hybridization to confirm ERG rearrangements and characterize PTEN deletion, as well as high-resolution melting curve analysis and Sanger sequencing to determine SPOP mutation status.RESULTSBased on index focus alone, ERG, SPINK1, PTEN, and SPOP alterations were identified in 47.5%, 10.8%, 14.3%, and 5.1% of RP specimens, respectively. In 233 multifocal RPs with ERG/SPINK1 status in all foci, 139 (59.7%) had discordant molecular alterations between foci. Collision tumors, as defined by discrepant ERG/SPINK1 status within a single focus, were identified in 29 (9.4%) RP specimens.CONCLUSIONInterfocal molecular heterogeneity was identified in about 60% of multifocal RP specimens, and collision tumors were present in about 10%. We present this phenomenon as a model for the intrafocal heterogeneity observed in previous studies and propose that future genomic studies screen for collision tumors to better characterize molecular heterogeneity.FUNDINGEarly Detection Research Network US National Cancer Institute (NCI) 5U01 CA111275-09, Center for Translational Pathology at Weill Cornell Medicine (WCM) Department of Pathology and Laboratory Medicine, US NCI (WCM SPORE in Prostate Cancer, P50CA211024-01), R37CA215040, Damon Runyon Cancer Research Foundation, US MetLife Foundation Family Clinical Investigator Award, Norwegian Cancer Society (grant 208197), and South-Eastern Norway Regional Health Authority (grant 2019016 and 2020063).
Cancer Stem Cells of Sarcoma (2013)

Sarcomas are malignant mesenchymal tumors. Mesenchymal tissue is defi ned as a complex of nonepithelial structures of the body exclusive of reproductive tissue, glia, and hematopoietic and lymphoid tissue. Embryonically, these nonepithelial structures are derived from the mesoderm and, to a lesser degree, from the neuroectoderm and are grouped into fi brous tissue, adipose tissue, skeletal muscle, blood and lymph vessels, and peripheral nervous tissue (Aogi et al. 2000). The word “sarcoma” is derived from the Greek word sarkoma meaning “fl eshy outgrowth”; sarcomas can present as either a bone sarcoma or a soft tissue sarcoma (Misra et al. 2009).
All-in-one magnetic resonance arthrography of the shoulder in a vertically open magnetic resonance unit (2008)

MR arthrography of the shoulder joint using a vertically open magnet can be performed as a single comprehensive test, including the injection and the static and dynamic motion MR imaging. Good diagnostic accuracy for intraarticular lesions and glenohumeral instability was found in a small sample.
Autocrine stimulation by estradiol-regulated growth factors of rat hormone-responsive mammary cancer: interaction with the polyamine pathway. (1986)

We have recently shown that the integrity of the polyamine pathway is essential but not sufficient for expression of the mitogenic effect of estradiol (E2) in the N-nitrosomethylurea-induced rat mammary tumor grown in vitro in the soft agar clonogenic assay. To elucidate the mechanism of E2 action in this system, we tested whether E2 may stimulate tumor growth through induction of secretory growth factor(s), as already proposed for human breast cancer cell lines in culture. Furthermore, we investigated the potential interaction between such "autocrine" control of tumor growth by E2 and the polyamine pathway. Conditioned medium obtained from E2-treated tumors (E2-CM) but not from control tumors (C-CM) consistently stimulated colony formation when added to N-nitrosomethylurea-mammary tumors plated in soft agar under serum-free media conditions. Such growth-promoting effects of the E2-CM was found to increase with increasing protein concentrations of the medium and was abolished by pretreatment of the medium with concanavalin A, heat, and trypsin. The addition of the polyamine biosynthetic inhibitor alpha-difluoromethylornithine (1 mM) totally abolished the colony-stimulating effect of the E2-CM. Exogenous administration of spermidine (0.1 mM) reversed the inhibitory effect of alpha-difluoromethylornithine on colony formation and restored the action of the E2-CM. Although the addition of polyamines alone did not affect the number of colonies formed, the administration of spermidine was found to significantly enhance in a dose-dependent fashion the colony-stimulating effect of suboptimal concentrations of E2-CM. Attempts to identify the E2-inducible growth factor in the E2-CM and in N-nitrosomethylurea-mammary tumor specimens using monoclonal antibodies raised against the Mr 52,000 E2-inducible protein gave negative results. We conclude that autocrine stimulation of tumor growth by E2 is not limited to human breast cancer cell lines but also occurs in individual experimental mammary tumors grown in soft agar. Our results show that the polyamines must be present for the expression of this "autocrine" control of tumor growth by E2. Finally, the identity of the E2-induced growth factor operating in our system remains to be determined.
Genetic Engineering of the Heme Pocket in Human Serum Albumin:  Modulation of O2 Binding of Iron Protoporphyrin IX by Variation of Distal Amino Acids (2007)

Complexing an iron protoporphyrin IX into a genetically engineered heme pocket of recombinant human serum albumin (rHSA) generates an artificial hemoprotein, which can bind O2 in much the same way as hemoglobin (Hb). We previously demonstrated a pair of mutations that are required to enable the prosthetic heme group to bind O2 reversibly: (i) Ile-142 → His, which is axially coordinated to the central Fe2+ ion of the heme, and (ii) Tyr-161 → Phe or Leu, which makes the sixth coordinate position available for ligand interactions [I142H/Y161F (HF) or I142H/Y161L (HL)]. Here we describe additional new mutations designed to manipulate the architecture of the heme pocket in rHSA−heme complexes by specifically altering distal amino acids. We show that introduction of a third mutation on the distal side of the heme (at position Leu-185, Leu-182, or Arg-186) can modulate the O2 binding equilibrium. The coordination structures and ligand (O2 and CO) binding properties of nine rHSA(triple mutant)−heme complexes have been physicochemically and kinetically characterized. Several substitutions were severely detrimental to O2 binding: for example, Gln-185, His-185, and His-182 all generated a weak six-coordinate heme, while the rHSA(HF/R186H)−heme complex possessed a typical bis-histidyl hemochrome that was immediately autoxidized by O2. In marked contrast, HSA(HL/L185N)−heme showed very high O2 binding affinity (P1/2O2 1 Torr, 22 °C), which is 18-fold greater than that of the original double mutant rHSA(HL)−heme and very close to the affinities exhibited by myoglobin and the high-affinity form of Hb. Introduction of Asn at position 185 enhances O2 binding primarily by reducing the O2 dissociation rate constant. Replacement of polar Arg-186 with Leu or Phe increased the hydrophobicity of the distal environment, yielded a complex with reduced O2 binding affinity (P1/2O2 9−10 Torr, 22 °C), which nevertheless is almost the same as that of human red blood cells and therefore better tuned to a role in O2 transport.
Combining retrosynthesis and mixed-integer optimization for minimizing the chemical inventory needed to realize a WHO essential medicines list (2020)

The access to essential medicines remains a problem in many low-income countries for logistic and expiration limits, among other factors. Enabling flexible replenishment and easier supply chain management by on demand manufacturing from stored starting materials provides a solution to this challenge. Recent developments in computer-aided chemical synthesis planning have benefited from machine learning in different aspects. In this manuscript, we use those techniques to perform a combined analysis of a WHO essential medicines list to identify synthetic routes that minimize chemical inventory that would be required to synthesize the all the active pharmaceutical ingredients. We use a synthesis planning tool to perform retrosynthetic analyses for 99 targets and solve a mixed-integer programming problem to select a combination of pathways that uses the minimal number of chemicals. This work demonstrates the technical feasibility of reducing storage of active pharmaceutical ingredients to a minimal inventory of starting materials.
A New Technique to Control Fines Migration in Poorly Consolidated Sandstones - Laboratory Development and Case Histories (2011)

Abstract Unconsolidated formations and high permeability reservoirs are susceptible to fines migration. The main contributing factors are high formation fluid velocity, wettability alteration, change in water salinity, and rock failure. Typically, fines migration problem occur in the near-wellbore vicinity due to high drawdown pressures. Depending on the severity, it can result in rapid productivity decline, erosion damage to downhole and/or surface hardware, and surface facility upsets. A properly designed frac pack frac pack can mitigate the migration of fines if it is indeed a problem. However, as insurance there are some technologies currently used to address fines migration in frac packs. These technologies have some limitation such as only being designed to treat the fracture but not the near-wellbore vicinity, prone to causing long-term damage to proppant pack conductivity, and needing remedial work to cleanup the proppant pack followed by retreatment. In this paper, we will discuss the development of a new technique that effectively controls the migration of fines both within the formation surrounding the near wellbore as well as fracture area, and which does not affect proppant pack conductivity. We first detail the laboratory testing program followed to develop this technology including synthetic pack fines migration core flow evaluation, compatibility with frac-pack fluids, proppant pack and formation damage. Thereafter, we discuss the field deployment process and compliment with case histories. The laboratory results demonstrate that fines migration in the synthetic pack is drastically reduced with this new technique, that the technique is applicable up to 280°F, and that it can be deployed in commonly used frac-pack fluids. Production results of treated frac-pack wells have met expectation and after a year no fines production has been reported.
In vitro tumor cell cytolysis mediated by peptide defensins of human and rabbit granulocytes (1986)

We examined the activity of defensins, cysteine-rich cationic peptides that are abundant in the cytoplasmic granules of human and rabbit granulocytes, against various tumor targets. The three human defensins, HNP-1, HNP-2, and HNP-3, lysed human and murine targets in chromium release and dye exclusion assays. Defensin-mediated tumor cell lysis was concentration-dependent, inhibited by serum, and dependent on temperature-sensitive events. Lysis was first detected by three hours of incubation and it reached a plateau between eight and 14 hours. In vitro exposure of murine teratocarcinoma cells to HNP 1-3 abrogated their oncogenicity in vivo. Nonmalignant target cells were also susceptible to defensin-mediated lysis. Four rabbit granulocyte defensins exerted marked (NP-1, NP-2) or moderate (NP-3a, NP-3b) cytotoxic activity, whereas defensin NP-5 was not cytotoxic. When tumor cells were incubated with human defensins in combination with hydrogen peroxide, synergistic cytotoxicity was detected. As defensins are released from granulocytes by various stimuli, their release could contribute to extracellular cytotoxicity which is independent of reactive oxygen intermediates.
A cell-based screening method using an intracellular antibody for discovering small molecules targeting the translocation protein LMO2 (2021)

Intracellular antibodies are tools that can be used directly for target validation by interfering with properties like protein-protein interactions. An alternative use of intracellular antibodies in drug discovery is developing small-molecule surrogates using antibody-derived (Abd) technology. We previously used this strategy with an in vitro competitive surface plasmon resonance method that relied on high-affinity antibody fragments to obtain RAS-binding compounds. We now describe a novel implementation of the Abd method with a cell-based intracellular antibody-guided screening method that we have applied to the chromosomal translocation protein LMO2. We have identified a chemical series of anti-LMO2 Abd compounds that bind at the same LMO2 location as the inhibitory anti-LMO2 intracellular antibody combining site. Intracellular antibodies could therefore be used in cell-based screens to identify chemical surrogates of their binding sites and potentially be applied to any challenging proteins, such as transcription factors that have been considered undruggable.
Pressure dependence of magnetoresistance for Fe/Cr multilayers (2006)

The magnetoresistance (MR) in Fe/Cr magnetic multilayers (MML) has been measured under high pressure up to 2.5 GPa. It is found that the spin-dependent scattering plays an important role in the pressure dependence of MR ratio. In the present work, for [Fe(20/spl Aring/)/Cr(10 /spl Aring/)]/sub 20/ MML with antiferromagnetic (AF) state, the pressure coefficient of saturation field H/sub s/ is (1/H/sub s/)(/spl part/H/sub s///spl part/P)=3.3/spl times/10/sup -2/ GPa/sup -1/ between 0.1 and 2.5 GPa. We found that the (1/|J|)(/spl part/|J|//spl part/P) for AF-Fe/Cr MML with polycrystalline structure is opposite in sign to that with epitaxial one. For [Fe(20 /spl Aring/)/Cr(22/spl Aring/)]/sub 20/ MML with ferromagnetic (F) state, anisotropic magnetoresistance (AMR) decreases with increasing pressure. It is suggested that the anisotropy constant decreases with weakening spin-orbit interaction at high pressure. At high field, the AMR is easily suppressed by applying pressure while the giant magnetoresistance around H/sub s/ increases slightly with increasing pressure for polycrystalline Fe/Cr MML.
Microfluidic Metasurface with High Tunability for Multi-Function: Dispersion Compensation and Beam Tracking (2016)

We present a microfluidic metasurface with high tunability composed of subwavelength C-shaped split ring resonators for multi-function. By accurately tuning each C-shaped split ring resonator, we demonstrate functions of dispersion-free beam steering, dispersion-free focusing and beam tracking.
Ellipsometry measurements on refractive index profiles of thin films (1990)

An ellipsometry technique for measuring the arbitrary refractive index profile of composite thin films is presented. The refractive index profile is obtained through a successive partitioning and computation process on measured data points with the aid of a phi /sub 0//T plot, which reduces errors. Analyses of the required number of data points in the partitioned sections, the errors caused by the inappropriate partitioning, and the cumulative errors are performed. A Delta phi /sub 0//T plot is used to monitor the overall cumulative errors of the computation. Experimental examples using this technique to measure the refractive index profile of O-N-O and O-N composite thin films are included and results are compared with those obtained by Auger electron spectroscopy. It is shown that this method is sensitive enough to determine the refractive index profile to a resolution of 20 AA.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Routing Strategies for High-Fidelity, Multiplexed Quantum Networks (2021)

We recently introduced a “quantum router” architecture that improves entanglement fidelities in chains of multiplexed repeaters. Here, we address local entanglement routing across general network graphs of routers to optimize entanglement rates and fidelities.
Detection of silicates in the Beta Pictoris disk (1991)

A broad 10-micron emission feature has been detected within 3 arcsec of the star Beta Pic which is known to have a circumstellar, possibly protoplanetary, disk. The observations were made using four narrow-band filters in the MSFC bolometer array at the IRTF. The emission feature closely resembles silicate features observed in Comets Halley and Kohoutek and in a variety of Galactic sources. The feature is strong, with the total flux density emitted by dust at 10.3 microns being at least twice the estimated continuum at that wavelength, and must be emitted by particles with characteristic radii less than 10 microns.
A Real-Time File System for Constrained Quality of Service Applications (2010)

The prevalence of multi-tuners, high-definition digital video recorder systems and home networking is increasing the number of simultaneous streams that must be processed by recorder storage devices. Whereas recent hard-disk drives provide enough performance to theoretically handle such workloads, general purpose file systems and I/O schedulers used by operating systems such as Linux do not satisfy the quality of service (QoS) requirements necessary for efficient processing of real-time video streams. In this paper, we introduce the Audio/Video File System (AVFS) composed of a file system and a disk I/O scheduler optimized for handling simultaneous high bit-rate real-time streams. Using a precise QoS measurement method, evaluation results of a Linux implementation of AVFS show that, compared to traditional file systems such as ext3 and JFS, AVFS provides QoS guarantees for real-time streams and more stable performance.
Automated field testing of a track-type tractor (2003)

During the design process, earthmoving manufacturers routinely subject machines to rigorous, long-term tests to ensure quality. Automating portions of the testing process can potentially reduce the cost and time to complete these tests. We present a system that guides a 175 horsepower track-type tractor (Caterpillar Model D6R XL) along a prescribed route, allowing simple tasks to be completed by the automated machine while more complex tasks, such as site clean up, are handled by an operator. Additionally, the machine can be operated manually or via remote control and observed over the internet using a remote supervisor program. We envision that safety would be handled using work procedures, multiple over-ride methods and a GPS fence. The current system can follow turns within a half meter and straight sections within a quarter meter. The controller hardware and software are integrated with existing on-board electronic modules and allow for portability. The current system successfully handles the challenges of a clutch-brake drive train and has the potential to improve control over test variables, lower testing costs and enable testing at higher speeds allowing for higher impact tests than a human operator can tolerate.
Augmentation of Sinecomitant Immunity in Mice by .GAMMA.-(9H-Purine-6-yl)thiomethyl L-Glutamate (6-MPG), a Water-Soluble Derivative of 6-Mercaptopurine. (1998)

Effects of the administration of gamma-(9H-purine-6-yl)thiomethyl L-glutamate (6-MPG), a water-soluble derivative of 6-mercaptopurine, on concomitant and sinecomitant immunity against the implanted MethA tumor were studied in BALB/c mice. In the concomitant immunity experiments, mice were intradermally inoculated with 1x10(5) MethA cells at the right inguinal region on day 0. In sinecomitant immunity experiments, mice were similarly inoculated on day -21, and the grown tumor was excised on day -11. Both the tumor-bearing and tumor-ectomized animals were re-inoculated with 3x10(6) MethA cells intradermally at the left inguinal region on day 10. Administration of 6-MPG (100 mg/kg, i.p.) on days 3 through 7 significantly inhibited growth of the re-inoculated tumor in both series of experiments. Cyclophosphamide, adriamycin, mitomycin C and cis-diamminedichloroplatinum (II) had no significant effect on the growth of the re-inoculated tumor in the tumor-ectomized mice. Spleen cells harvested from the 6-MPG-treated tumor-ectomized mice showed a strong tumor-neutralizing activity (Winn assay).
Model-based Safety Monitoring of Product Flow Paths (2011)

Product flow paths are the routes that products take while flowing through a plant. The development of systems that ensure and monitor the correct and safe transport of material is usually plant-specific and based on informal knowledge, and is time-consuming and errorprone. In this work we seek a synthesis solution for the task of monitoring the safety of product flow paths in processing plants. A formal model of the plant is used, which defines a simplified plant representation that considers the possibility of flow through its elements. Based on this model, we present a formalisation of the safety of a product flow path at a given plant state. This formulation may be used as a guideline for automating the construction of systems which perform safety monitoring of product flow paths. An outline for the design of such a system following a decentralisation scheme is also presented.
Human immunodeficiency virus type 1 Tat activity in human neuronal cells: uptake and trans-activation (1994)

Neurological dysfunction in AIDS occurs in the absence of productive infection of neurons, and may involve modulation of neuronal cell function by viral or cellular products released from surrounding infected cells. The human immunodeficiency virus type 1 (HIV-1) trans-activator protein Tat may be one such factor, as it can act as a neurotoxin, induces marked morphological changes in neurons and astrocytes in primary embryonic rodent brain cultures, and is released by certain HIV-1-infected cells. In addition, Tat can alter expression of cellular genes in several non-neuronal cell types. To explore the possibility that Tat may also mediate neuronal dysfunction in AIDS through non-lethal effects on neurons, we determined the trans-activating ability of Tat in human neuronal cells. We generated human neuronal cell lines stably expressing several HIV-1 tat genes, and also tested human neuronal cells exposed to extracellular recombinant Tat protein. Both endogenously expressed Tat as well as exogenous recombinant Tat protein up-regulated HIV-1 long terminal region (LTR)-driven gene expression by several hundred-fold. Only brief exposure to recombinant Tat was necessary and no toxic effects were seen at levels sufficient for trans-activation. Furthermore, Tat significantly enhanced virus expression in neuronal cells transfected with molecular clones of HIV-1. These results show that Tat is trans-activationally active in human neuronal cells, and can be taken up from the extracellular compartment by these cells in a biologically active form. Neurons represent an important potential target for Tat-mediated cellular dysfunction.