gebhart/patrepeval huggingface dataset:
Label-free visualization and characterization of extracellular vesicles in breast cancer (2019)

Despite extensive interest, extracellular vesicle (EV) research remains technically challenging. One of the unexplored gaps in EV research has been the inability to characterize the spatially and functionally heterogeneous populations of EVs based on their metabolic profile. In this paper, we utilize the intrinsic optical metabolic and structural contrast of EVs and demonstrate in vivo/in situ characterization of EVs in a variety of unprocessed (pre)clinical samples. With a pixel-level segmentation mask provided by the deep neural network, individual EVs can be analyzed in terms of their optical signature in the context of their spatial distribution. Quantitative analysis of living tumor-bearing animals and fresh excised human breast tissue revealed abundance of NAD(P)H-rich EVs within the tumor, near the tumor boundary, and around vessel structures. Furthermore, the percentage of NAD(P)H-rich EVs is highly correlated with human breast cancer diagnosis, which emphasizes the important role of metabolic imaging for EV characterization as well as its potential for clinical applications. In addition to the characterization of EV properties, we also demonstrate label-free monitoring of EV dynamics (uptake, release, and movement) in live cells and animals. The in situ metabolic profiling capacity of the proposed method together with the finding of increasing NAD(P)H-rich EV subpopulations in breast cancer have the potential for empowering applications in basic science and enhancing our understanding of the active metabolic roles that EVs play in cancer progression.
Synthesis and Antiviral and Fungicidal Activity Evaluation of β-Carboline, Dihydro-β-carboline, Tetrahydro-β-carboline Alkaloids, and Their Derivatives (2014)

Six known β-carboline, dihydro-β-carboline, and tetrahydro-β-carboline alkaloids and a series of their derivatives were designed, synthesized, and evaluated for their anti-tobacco mosaic virus (TMV) and fungicidal activities for the first time. All of the alkaloids and some of their derivatives (compounds 3, 4, 14, and 19) exhibited higher anti-TMV activity than the commercial antiviral agent Ribavirin both in vitro and in vivo. Especially, the inactivation, curative, and protection activities of alkaloids Harmalan (62.3, 55.1, and 60.3% at 500 μg/mL) and tetrahydroharmane (64.2, 57.2, and 59.5% at 500 μg/mL) in vivo were much higher than those of Ribavirin (37.4, 36.2, and 38.5% at 500 μg/mL). A new derivative, 14, with optimized physicochemical properties, obviously exhibited higher activities in vivo (50.4, 43.9, and 47.9% at 500 μg/mL) than Ribavirin and other derivatives; therefore, 14 can be used as a new lead structure for the development of anti-TMV drugs. Moreover, most of these compounds exhibited good fungicidal activity against 14 kinds of fungi, especially compounds 4, 7, and 11.
Application of immunohistochemistry and in situ hybridization for detection of bovine coronavirus in paraffin-embedded, formalin-fixed intestines (1997)

A monoclonal antibody (MAb) (Z3A5) against spike protein subunit of bovine coronavirus (BCV) reacted with the virus in formalin-fixed intestines in an immunoperoxidase test. We found an 88% correlation between immunohistochemistry with Z3A5 and in situ hybridization with a BCV nucleoprotein cDNA probe. MAb Z3A5 reacted with 90 BCV isolates from the United States and was an effective reagent for the diagnosis of BCV.
New polyolefin elastomers from metallocenes (1995)

Abstract In this paper, new polyolefin elastomers, obtained from metallocene based catalytic systems, are presented. The potentialities of metallocenes for the preparation of polyolefin elastomers are discussed with reference to the traditional vanadium and titanium based catalysts. The role played by a Ziegler ‐ Natta catalyst, either stereospecific or aspecific, is discussed.
Material Characterization and Flaw Detection, Sizing, and Location by the Differential Gamma Scattering Spectroscopy Technique. Part I: Development of Theoretical Basis (1990)

The differential gamma scattering spectroscopy technique is a novel means of nondestructive testing using Compton scattering to determine local density perturbations in a test sample. The test sample is irradiated with a narrow collimated beam of gamma rays, and the scattered radiation field is detected in a transversely placed high-purity germanium detector. The detector provides excellent energy resolution so that a detailed energy spectrum can be obtained. This spectrum is then subtracted from a reference spectrum that was collected from a well-known, unflawed sample to obtain the differential spectrum. This differential spectrum primarily contains information characterizing the flaw. Using the relationship between the scattering angle and the scattering energy that characterizes Compton scattering, the single-scattered spectrum can be used to determine the location of scattering and, consequently, the density distribution along the portion of the primary beam path that passes through the sample. An attractive feature of this technique that sets it apart from other Compton scattering techniques is the ability to detect flaws both on and off the primary beam path.
Synthesis of a new energetic nitrate ester (2024)

Nitrate esters have been known as useful energetic materials since the discovery of nitroglycerin by Ascanio Sobrero in 1846. The development of methods to increase the safety and utility of nitroglycerin by Alfred Nobel led to the revolutionary improvement in the utility of nitroglycerin in explosive applications in the form of dynamite. Since then, many nitrate esters have been prepared and incorporated into military applications such as double-based propellants, detonators and as energetic plasticizers. Nitrate esters have also been shown to have vasodilatory effects in humans and thus have been studied and used for treatments of ailments such as angina. The mechanism of the biological response towards nitrate esters has been elucidated recently. Interestingly, many of the nitrate esters used for military purposes are liquids (ethylene glycol dinitrate, propylene glycol dinitrate, etc). Pentaerythritol tetranitrate (PETN) is one of the only solid nitrate esters, besides nitrocellulose, that is used in any application. Unfortunately, PETN melting point is above 100 {sup o}C, and thus must be pressed as a solid for detonator applications. A more practical material would be a melt-castable explosive, for potential simplification of manufacturing processes. Herein we describe the synthesis of a new energetic nitrate ester (1) that is a solid at ambient temperatures, has a melting point of 85-86 {sup o}C and has the highest density of any known nitrate ester composed only of carbon, hydrogen, nitrogen and oxygen. We also describe the chemical, thermal and sensitivity properties of 1 as well as some preliminary explosive performance data.
Efficient elimination of false positives using static analysis (2015)

Bug detection using static analysis has been found useful in practice for ensuring software quality and reliability. However, it often requires sifting through a large number of warnings. This can be handled by generating an assertion corresponding to each warning and verifying the assertion using a model checker to classify the warning as an error or a false positive. Since model checking over larger code fragments is non-scalable and expensive, it is useful to model check a given assertion with a small calling context length. For this, the variables receiving values from outside the context are initialized with arbitrary values generated by non-deterministic choice functions. The calling context length is then gradually increased on a need basis to include callers higher up in the call chains. While this aids scalability by keeping the calling context as small as possible, it requires multiple calls to model checker for the same assertion, requiring a considerable amount of time. We present a static analysis to expedite false positive elimination. It is based on the following observation: When the variables involved in an assertion are allowed to take arbitrary values at the point of assertion, the assertion is most likely to be violated by some or the other combination of values. In such cases, usage of a model checker is redundant as it does not aid in resolution of the corresponding warning. Our data flow analysis identifies (an over-approximated set of) such variables using a novel lattice so that model checking of assertions involving such variables can be avoided. Our empirical evaluation demonstrates that, on an average, the proposed static analysis avoids 49.49% of the total model checking calls, and it reduces the false positives elimination time by 39.28%. However, this gain is achieved at the cost of missing 2.78% false positives which could have been eliminated otherwise.
Novel Target for Peptide-Based Imaging and Treatment of Brain Tumors (2014)

Malignant gliomas are associated with high mortality due to infiltrative growth, recurrence, and malignant progression. Even with the most efficient therapy combinations, median survival of the glioblastoma multiforme (grade 4) patients is less than 15 months. Therefore, new treatment approaches are urgently needed. We describe here identification of a novel homing peptide that recognizes tumor vessels and invasive tumor satellites in glioblastomas. We demonstrate successful brain tumor imaging using radiolabeled peptide in whole-body SPECT/CT imaging. Peptide-targeted delivery of chemotherapeutics prolonged the lifespan of mice bearing invasive brain tumors and significantly reduced the number of tumor satellites compared with the free drug. Moreover, we identified mammary-derived growth inhibitor (MDGI/H-FABP/FABP3) as the interacting partner for our peptide on brain tumor tissue. MDGI was expressed in human brain tumor specimens in a grade-dependent manner and its expression positively correlated with the histologic grade of the tumor, suggesting MDGI as a novel marker for malignant gliomas.
Macrocyclic peptides decrease c-Myc protein levels and reduce prostate cancer cell growth (2017)

The oncoprotein c-Myc is often overexpressed in cancer cells, and the stability of this protein has major significance in deciding the fate of a cell. Thus, targeting c-Myc levels is an attractive approach for developing therapeutic agents for cancer treatment. In this study, we report the anti-cancer activity of the macrocyclic peptides [D-Trp]CJ-15,208 (cyclo[Phe-D-Pro-Phe-D-Trp]) and the natural product CJ-15,208 (cyclo[Phe-D-Pro-Phe-Trp]). [D-Trp]CJ-15,208 reduced c-Myc protein levels in prostate cancer cells and decreased cell proliferation with IC<sub>50</sub> values ranging from 2.0 to 16 µM in multiple PC cell lines. [D-Trp]CJ-15,208 induced early and late apoptosis in PC-3 cells following 48 hours treatment, and growth arrest in the G2 cell cycle phase following both 24 and 48 hours treatment. Down regulation of c-Myc in PC-3 cells resulted in loss of sensitivity to [D-Trp]CJ-15,208 treatment, while overexpression of c-Myc in HEK-293 cells imparted sensitivity of these cells to [D-Trp]CJ-15,208 treatment. This macrocyclic tetrapeptide also regulated PP2A by reducing the levels of its phosphorylated form which regulates the stability of cellular c-Myc protein. Thus [D-Trp]CJ-15,208 represents a new lead compound for the potential development of an effective treatment of prostate cancer.
Fluorinated counterion-enhanced emission of rhodamine aggregates: ultrabright nanoparticles for bioimaging and light-harvesting (2015)

The key to ultrabright fluorescent nanomaterials is the control of dye emission in the aggregated state. Here, lipophilic rhodamine B derivatives are assembled into nanoparticles (NPs) using tetraphenylborate counterions with varied fluorination levels that should tune the short-range dye ordering. Counterion fluorination is found to drastically enhance the emission characteristics of these NPs. Highly fluorinated counterions produce 10-20 nm NPs containing >300 rhodamine dyes with a fluorescence quantum yield of 40-60% and a remarkably narrow emission band (34 nm), whereas, for other counterions, aggregation caused quenching with a weak broad-band emission is observed. NPs with the most fluorinated counterion (48 fluorines) are ∼40-fold brighter than quantum dots (QD585 at 532 nm excitation) in single-molecule microscopy, showing improved photostability and suppressed blinking. Due to exciton diffusion, revealed by fluorescence anisotropy, these NPs are efficient FRET donors to single cyanine-5 acceptors with a light-harvesting antenna effect reaching 200. Finally, NPs with the most fluorinated counterion are rather stable after entry into living cells, in contrast to their less fluorinated analogue. Thus, the present work shows the crucial role of counterion fluorination in achieving high fluorescence brightness and photostability, narrow-band emission, efficient energy transfer and high intracellular stability of nanomaterials for light harvesting and bioimaging applications.
XENOGENEIC THYMIC TRANSPLANTATION IN A PIG-TO-NON-HUMAN-PRIMATE MODEL (1998)

464 Previous work from our laboratory has demonstrated the importance of the thymus for rapid and stable induction of tolerance to allogeneic renal transplants. Recently, xenogeneic cellular tolerance was demonstrated in a rodent model following fetal porcine thymic tissue grafting. We now attempt to extend this approach of thymic transplantation in a porcine to non-human-primate system. Methods: Adult cynomolgus monkeys underwent a conditioning regimen including thymectomy, splenectomy, low-dose whole body irradiation(150R) and T cell depletion using FN18-CRM9 (a conjugate of an anti CD3-antibody and a mutant diphtheria toxin). Porcine thymic tissue from a second trimester litter was then transplanted into the left quadriceps muscle of the recipient (n=1). T cell depletion and subsequent reconstitution in blood and lymphnodes was assessed by FACS analyses and histology. Engraftment of thymic tissue was followed by histology. For examination of cellular responses, mixed lymphocyte reactions (MLR) were performed. Results:(1) No untoward side effects of the procedure were observed; (2) T cell depletion reached a maximum of 99% in the peripheral blood at day 4 after administration of FN18-CRM9; (3) reconstitution of T cells was observed starting from day 6 post-thymic transplant, leading to full reconstitution by day 27. FACS analyses showed that the reconstituting cells expressed CD3+CD45RA+ surface markers; (4) transient pig cell chimerism was observed in the thymic transplant recipient on postoperative day 15; (5) MLR assays demonstrated hyporesponsiveness to xenogeneic SLA-matched porcine stimulators up to 69 days post thymic transplant; (6) levels of natural antibodies (IgM) against the α(1,3)gal-epitope decreased gradually after thymic transplantation up to day 117; and (7) although biospies revealed rejection of the thymic tissue, initial T cell reconstitution, chimerism and xenogeneic hyporeponsiveness may have been induced by the thymic graft prior to its rejection. A control animal not receiving a thymic transplant is needed to confirm such a role for the thymus and is currently in progress.Conclusions: These data indicate that porcine thymic tissue transplanted intramuscularly into T cell depleted non-human primates is able to engraft, at least for a short period, and may contribute to the regeneration of tolerant T cells. Therefore, this model may provide a means of inducing xenograft tolerance in the pig to primate combination.
A new Gamma Knife<sup>®</sup> radiosurgery paradigm: Tomosurgery (2007)

This study proposes and simulates an inverse treatment planning and a continuous dose delivery approach for the Leksell Gamma Knife (LGK, Elekta, Stockholm, Sweden) which we refer to as "Tomosurgery." Tomosurgery uses an isocenter that moves within the irradiation field to continuously deliver the prescribed radiation dose in a raster-scanning format, slice by slice, within an intracranial lesion. Our Tomosurgery automated (inverse) treatment planning algorithm utilizes a two-stage optimization strategy. The first stage reduces the current three-dimensional (3D) treatment planning problem to a series of more easily solved 2D treatment planning subproblems. In the second stage, those 2D treatment plans are assembled to obtain a final 3D treatment plan for the entire lesion. We created Tomosurgery treatment plans for 11 patients who had already received manually-generated LGK treatment plans to treat brain tumors. For the seven cases without critical structures (CS), the Tomosurgery treatment plans showed borderline to significant improvement in within-tumor dose standard deviation (STD) (p <0.058, or p <0.011 excluding case 2) and conformality (p < 0.042), respectively. In three of the four cases that presented CS, the Tomosurgery treatment plans showed no statistically significant improvements in dose conformality (p <0.184), and borderline significance in improving within-tumor dose homogeneity (p <0.054); CS damage measured by V20 or V30 (i.e., irradiated CS volume that receives > or =20% or > or =30% of the maximum dose) showed no significant improvement in the Tomosurgery treatment plans (p<0.345 and p <0.423, respectively). However, the overall CS dose volume histograms were improved in the Tomosurgery treatment plans. In addition, the LGK Tomosurgery inverse treatment planning required less time than standard of care, forward (manual) LGK treatment planning (i.e., 5-35 min vs 1-3 h) for all 11 cases. We expect that LGK Tomosurgery will speed treatment planning and improve treatment quality, especially for large and/or geometrically complex lesions. However, using only 4 mm collimators could greatly increase treatment plan delivery time for a large brain lesion. This issue is subject to further investigation.
Multivariable Recursive Subspace Identification with Application to Artificial Pancreas Systems (2017)

Designing a fully automated artificial pancreas (AP) system is challenging. Changes in the glucose-insulin dynamics in the human body over time, and the inter-subject and day-to-day variability of people with type 1 diabetes (T1D) are two important factors that would highly undermine the performance of an AP that is based on time-invariant and non-individualized models. People with T1D show different responses to carbohydrate intake, insulin, physical activity and stress with day-to-day variability present between or within specific patients. Thus, the control law in an AP system requires a reliable time-varying individualized model to perform efficiently. In this work, a novel recursive identification approach called a Predictor-Based Subspace Identification (PBSID) method is used for identifying a linear time-varying glucose-insulin model for each individual. Model identification and validation are based on clinical data from closed-loop experiments. The models are evaluated by means of various performances indices: Variance Accounted For (VAF), Root mean square error (RMSE), Normalized root mean square error (NRMSE) and Normalized mean square error (NMSE). The proposed method provides a stable time-varying state space model over time. It can be also individualized for each patient by defining the order of the system correctly. The approach proposed in this work has shown a strong potential to identify a consistent glucose-insulin model in real time for use in an AP system.
HELIOS (2010)

Fast growing traffic for both the Internet and within data centers has lead to an increasing demand for high-speed switching systems. In this paper, we propose a fully distributed scheduling algorithm with an O(1) complexity, for a switch with an optical switching fabric. The inputs only use local queue information to make their scheduling decisions, and the switch consumes much less power than an electronic switch. Therefore, we call the switch HELIOS: High Energy-efficiency Locally-scheduled Input-queued Optical Switch. HELIOS can achieve 100% throughput for any admissible Bernoulli i.i.d traffic. To our knowledge, this is the first distributed scheduling algorithm to guarantee 100% throughput for an input-queued optical switch.
Position dependent prediction combination for intra-frame video coding (2016)

Intra-frame prediction in the High Efficiency Video Coding (HEVC) standard can be empirically improved by applying sets of recursive two-dimensional filters to the predicted values. However, this approach does not allow (or complicates significantly) the parallel computation of pixel predictions. In this work we analyze why the recursive filters are effective, and use the results to derive sets of non-recursive predictors that have superior performance. We present an extension to HEVC intra prediction that combines values predicted using non-filtered and filtered (smoothed) reference samples, depending on the prediction mode, and block size. Simulations using the HEVC common test conditions show that a 2.0% bit rate average reduction can be achieved compared to HEVC, for All Intra (AI) configurations.
Equalization of Third-Order Intermodulation Products in Wideband Direct Conversion Receivers (2008)

This paper reports a SAW-less direct-conversion receiver which utilizes a mixed-signal feedforward path to regenerate and adaptively cancel IM3 products, thus accomplishing system-level linearization. The receiver system performance is dominated by a custom integrated RF front end implemented in 130-nm CMOS and achieves an uncorrected out-of-band IIP3 of -7.1 dBm under the worst-case UMTS FDD Region 1 blocking specifications. Under IM3 equalization, the receiver achieves an effective IIP3 of +5.3 dBm and meets the UMTS BER sensitivity requirement with 3.7 dB of margin.
Grain growth in Al alloy conductors as a result of rapid annealing (1984)

Aluminum and aluminum alloy thin films were rapidly annealed using high intensity visible light. Under suitable conditions, substantial grain growth was achieved in the Al-Cu and Al-Si-Cu conductors and this grain growth had a beneficial effect on electromigration. Unfortunately, this growth did not occur uniformily across the wafer. A second phenomenon, which resulted from thermal cycling, was the solid phase reduction of SiO2 by the overlying Al film.
Type II collagen degradation in spontaneous osteoarthritis in C57BL/6 and BALB/c mice (1999)

These results indicate that type II collagen degradation in spontaneous murine OA is associated with degeneration and is a localized, instead of a generalized, process.
Tactile rendering of 3D features on touch surfaces (2013)

We present a tactile-rendering algorithm for simulating 3D geometric features, such as bumps, on touch screen surfaces. This is achieved by modulating friction forces between the user's finger and the touch screen, instead of physically moving the touch surface. We proposed that the percept of a 3D bump is created when local gradients of the rendered virtual surface are mapped to lateral friction forces. To validate this approach, we first establish a psychophysical model that relates the perceived friction force to the controlled voltage applied to the tactile feedback device. We then use this model to demonstrate that participants are three times more likely to prefer gradient force profiles than other commonly used rendering profiles. Finally, we present a generalized algorithm and conclude the paper with a set of applications using our tactile rendering technology.