gebhart/patrepeval huggingface dataset:
Beyond Antiresorptive Activity: Risedronate-Based Coordination Complexes To Potentially Treat Osteolytic Metastases (2023)

Coordination of clinically employed bisphosphonate, risedronate (RISE), to bioactive metals, Ca<sup>2+</sup>, Mg<sup>2+</sup>, and Zn<sup>2+</sup>, allowed the formation of bisphosphonate-based coordination complexes (BPCCs). Three RISE-based BPCCs, RISE-Ca, RISE-Mg, and RISE-Zn, were produced, and their structures were elucidated by single crystal X-ray diffraction. Interestingly, the addition of an auxiliary ligand, etidronic acid (HEDP), resulted in the recrystallized protonated form of the ligand, H-RISE. The pH-dependent structural stability of the RISE-based BPCCs was measured by means of dissolution profiles under neutral and acidic simulated physiological conditions (PBS and FaSSGF, respectively). In comparison to RISE (<i>Actonel</i>), the complexes showed a lower equilibrium solubility (∼70-85% in 18-24 h) in PBS, while a higher equilibrium solubility (∼100% in 3 h) in acidic media. The results point to the capacity to release this BP in a pH-dependent manner from the RISE-based BPCCs. Subsequently, the particle size of RISE-Ca was reduced, from 300 μm to ∼350 d.nm, employing the phase inversion temperature (PIT)-nanoemulsion method, resulting in <i>nano</i>-Ca@RISE. Aggregation measurements of <i>nano</i>-Ca@RISE in 1% fetal bovine serum (FBS):H<sub>2</sub>O was monitored after 24, 48, and 72 h to study the particle size longevity in physiological media, showing that the suspended material has the potential to maintain its particle size over time. Furthermore, binding assays were performed to determine the potential binding of <i>nano</i>-Ca@RISE to the bone, where results show higher binding (∼1.7×) for the material to hydroxyapatite (HA, 30%) when compared to RISE (17%) in 1 d. The cytotoxicity effects of <i>nano</i>-Ca@RISE were compared to those of RISE against the human breast cancer MDA-MB-231 and normal osteoblast-like hFOB 1.19 cell lines by dose-response curves and relative cell viability assays in an <i>in vitro</i> setting. The results demonstrate that <i>nano</i>-Ca@RISE significantly decreases the viability of MDA-MB-231 with high specificity, at concentrations ∼2-3× lower than the ones reported employing other third-generation BPs. This is supported by the fact that when normal osteoblast cells (hFOB 1.19), which are part of the tissue microenvironment at metastatic sites, were treated with <i>nano</i>-Ca@RISE no significant decrease in viability was observed. This study expands on the therapeutic potential of RISE beyond its antiresorptive activity through the design of BPCCs, specifically <i>nano</i>-Ca@RISE, that bind to the bone and degrade in a pH-dependent manner under acidic conditions.
Downregulation of Caffeic Acid 3-<i>O</i>-Methyltransferase and Caffeoyl CoA 3-<i>O</i>-Methyltransferase in Transgenic Alfalfa: Impacts on Lignin Structure and Implications for the Biosynthesis of G and S Lignin (2001)

Transgenic alfalfa plants were generated harboring caffeic acid 3-O-methyltransferase (COMT) and caffeoyl CoA 3-O-methyltransferase (CCOMT) cDNA sequences under control of the bean phenylalanine ammonia-lyase PAL2 promoter. Strong downregulation of COMT resulted in decreased lignin content, a reduction in total guaiacyl (G) lignin units, a near total loss of syringyl (S) units in monomeric and dimeric lignin degradation products, and appearance of low levels of 5-hydroxy guaiacyl units and a novel dimer. No soluble monolignol precursors accumulated. In contrast, strong downregulation of CCOMT led to reduced lignin levels, a reduction in G units without reduction in S units, and increases in beta-5 linked dimers of G units. Accumulation of soluble caffeic acid beta-d-glucoside occurred only in CCOMT downregulated plants. The results suggest that CCOMT does not significantly contribute to the 3-O-methylation step in S lignin biosynthesis in alfalfa and that there is redundancy with respect to the 3-O-methylation reaction of G lignin biosynthesis. COMT is unlikely to catalyze the in vivo methylation of caffeic acid during lignin biosynthesis.
Fabrication of a Monolithic Implantable Neural Interface from Cubic Silicon Carbide (2019)

One of the main issues with micron-sized intracortical neural interfaces (INIs) is their long-term reliability, with one major factor stemming from the material failure caused by the heterogeneous integration of multiple materials used to realize the implant. Single crystalline cubic silicon carbide (3C-SiC) is a semiconductor material that has been long recognized for its mechanical robustness and chemical inertness. It has the benefit of demonstrated biocompatibility, which makes it a promising candidate for chronically-stable, implantable INIs. Here, we report on the fabrication and initial electrochemical characterization of a nearly monolithic, Michigan-style 3C-SiC microelectrode array (MEA) probe. The probe consists of a single 5 mm-long shank with 16 electrode sites. An ~8 µm-thick p-type 3C-SiC epilayer was grown on a silicon-on-insulator (SOI) wafer, which was followed by a ~2 µm-thick epilayer of heavily n-type (n<sup>+</sup>) 3C-SiC in order to form conductive traces and the electrode sites. Diodes formed between the p and n<sup>+</sup> layers provided substrate isolation between the channels. A thin layer of amorphous silicon carbide (<i>a</i>-SiC) was deposited via plasma-enhanced chemical vapor deposition (PECVD) to insulate the surface of the probe from the external environment. Forming the probes on a SOI wafer supported the ease of probe removal from the handle wafer by simple immersion in HF, thus aiding in the manufacturability of the probes. Free-standing probes and planar single-ended test microelectrodes were fabricated from the same 3C-SiC epiwafers. Cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were performed on test microelectrodes with an area of 491 µm<sup>2</sup> in phosphate buffered saline (PBS) solution. The measurements showed an impedance magnitude of 165 kΩ ± 14.7 kΩ (mean ± standard deviation) at 1 kHz, anodic charge storage capacity (CSC) of 15.4 ± 1.46 mC/cm<sup>2</sup>, and a cathodic CSC of 15.2 ± 1.03 mC/cm<sup>2</sup>. Current-voltage tests were conducted to characterize the p-n diode, n-p-n junction isolation, and leakage currents. The turn-on voltage was determined to be on the order of ~1.4 V and the leakage current was less than 8 μA<sub>rms</sub>. This all-SiC neural probe realizes nearly monolithic integration of device components to provide a likely neurocompatible INI that should mitigate long-term reliability issues associated with chronic implantation.
Diamond in the rough (2004)

Data items archived in data warehouses or those that arrive online as streams typically have attributes which take values from multiple hierarchies (e.g., time and geographic location; source and destination IP addresses). Providing an aggregate view of such data is important to summarize, visualize, and analyze. We develop the aggregate view based on certain hierarchically organized sets of large-valued regions ("heavy hitters"). Such Hierarchical Heavy Hitters (HHHs) were previously introduced as a crucial aggregation technique in one dimension. In order to analyze the wider range of data warehousing applications and realistic IP data streams, we generalize this problem to multiple dimensions.We identify and study two variants of HHHs for multi-dimensional data, namely the "overlap" and "split" cases, depending on how an aggregate computed for a child node in the multi-dimensional hierarchy is propagated to its parent element(s). For data warehousing applications, we present offline algorithms that take multiple passes over the data and produce the exact HHHs. For data stream applications, we present online algorithms that find approximate HHHs in one pass, with provable accuracy guarantees.We show experimentally, using real and synthetic data, that our proposed online algorithms yield outputs which are very similar (virtually identical, in many cases) to their offline counterparts. The lattice property of the product of hierarchical dimensions ("diamond") is crucially exploited in our online algorithms to track approximate HHHs using only a small, fixed number of statistics per candidate node, regardless of the number of dimensions.
EGFR-SGLT1 interaction does not respond to EGFR modulators, but inhibition of SGLT1 sensitizes prostate cancer cells to EGFR tyrosine kinase inhibitors (2013)

These data suggest that EGFR in cancer cells can exist as either a tyrosine kinase modulator responsive status or an irresponsive status. SGLT1 is a protein involved in EGFR's functions that are irresponsive to EGFR tyrosine kinase inhibitors and, therefore, the EGFR-SGLT1 interaction might be a novel target for prostate cancer therapy.
Changing pitch and duration in LPC synthesized speech using multipulse excitation (1983)

Pitch and duration changes are fairly simple to realize in pitch-excited LPC vocoders. Recent work [Atal and Remde, Proc. ICASSP 82, pp. 614–617) has shown that use of multi-pulse excitation provides a significant improvement in the quality of synthetic speech. However, procedures for changing pitch with multi-pulse excitation are not known. We discuss methods for introducing pitch and duration changes in speech synthesized with multi-pulse excitation. Pitch is changed by modifying the length of individual pitch periods. Two methods of adjusting the period length were investigated: one by linear scaling of the time axis of the multi-pulse excitation, the other, by adding or deleting zeros in the excitation. The second method produced very little distortion in the synthetic speech, except in those cases where there was a significant interaction between the first formant and the pitch frequency. The scaling of the time axis produced significantly more distortion. Duration changes are accomplished by adding or removing pitch periods. The LPC area parameters and the amplitude of the major excitmion pulse are interpolated as necessary in creating additional pitch periods.
Sm‐p80–Based DNA Vaccine Provides Baboons with Levels of Protection against<i>Schistosoma</i><i>mansoni</i>Infection Comparable to Those Achieved by the Irradiated Cercarial Vaccine (2010)

To date, no vaccine is available to prevent human schistosomiasis. We have targeted a protein of Schistosoma mansoni that plays an important role in the surface membrane renewal process, a mechanism widely believed to be utilized by the parasite as an immune evasion strategy. Sm-p80 antigen is a promising vaccine target because of its documented immunogenicity, protective efficacy, and antifecundity effects observed in both experimental murine and nonhuman primate models of this infectious disease. In the present study, we report that, in a vector approved for human use (VR1020), an Sm-p80-based DNA vaccine formulation confers a 46% reduction in the worm burden in a baboon (Papio anubis) model. Baboons vaccinated with Sm-p80-VR1020 had a 28% decrease in egg production after challenge with the infectious parasite. Sm-p80-VR1020 vaccine elicited robust immune responses to specific antigen Sm-p80, including immunoglobulin (Ig) G, its subtypes IgG1 and IgG2, and IgA and IgM in vaccinated animals. When stimulated in vitro with recombinant Sm-p80, peripheral blood mononuclear cells and splenocytes from baboons vaccinated with Sm-p80-VR1020 produced considerably higher levels of T helper 1 response-enhancing cytokines (interleukin [IL]-2 and interferon-gamma) than T helper 2 (Th2) response-enhancing cytokines (IL-4 and IL-10). Peripheral blood mononuclear cells produced a significantly higher number of spot-forming units for interferon-gamma than for IL-4 in enzyme-linked immunosorbent spot assays. A mixed T helper 1/T helper 2 type of humoral and T cell responses was generated after immunization with Sm-p80-VR1020. These findings again highlight the potential of Sm-p80 as a promising vaccine candidate for schistosomiasis.
Strain-Tunable Chemiresistor (2010)

We have developed a resistance-based chemical sensor (chemiresistor) for volatile organic compounds whose sensitivity can be reversibly increased over a range of nearly 2 decades by the application of tensile strain. This polymer-based sensor is comprised of Au-plated magnetic particles structured into conducting chains by the application of a magnetic field during the curing of the prepolymer resin. The resistance of this field-structured composite increases when an analyte vapor swells the polymer and reduces the contact pressure between particles. We have found that applying a tensile strain increases both the sensor resistance and sensitivity, as defined by its relative resistance change. This increase in sensitivity is a smooth, continuous function of the applied strain, and the effect is fully reversible. Sensitivity tuning enables the response curve of the sensor to be dynamically optimized for sensing analytes over a wide concentration range.
A Critical Analysis of Valve-Compensated Hydrostatic Actuators: Qualitative Investigation (2019)

Hydrostatic actuation has gained interest from both academia and industry due to the unquestionable energetic advantages when compared to valve-controlled actuators; the main feature being the absence of throttling losses due to the direct control of the cylinder by the pump. However, the fact that the great majority of applications are based on single-rod cylinders has been both a challenge and a source of inspiration for a variety of different circuit designs. In an attempt to compensate for the uneven flows coming in and out of differential cylinders, several solutions have been proposed, including the use of hydraulic transformers, individual pumps connected to the cylinder ports or pumps with unmatched input and output flows. The simplest approach, however, seems to be the use of compensation valves in the circuit, which is the focus of this paper. Here, we analyse some representative circuits proposed along the years in a direct and elucidative manner, showing that the definitive solution to the single-rod actuator control problem has been established, paving the road for introducing stable and trustworthy circuits, which can be commercially used in the near future.
Fault signature modeling and detection of inner race bearing faults (2005)

This research develops a fault signature model and fault detection scheme for using machine vibration to detect inner race defects. To motivate this research, it is explained and illustrated with experimental results why fault signatures from non-outer race defects (e.g., inner race defects) can be less salient than those from outer race defects. Afterwards, a signal model is presented for the production and propagation of an inner race fault signature; this model is then used to design an inner race fault detection scheme. This scheme examines machine vibration spectra for peaks with phase coupled sidebands occurring at a spacing predicted by the model. The proficiency of this fault detection scheme at detecting inner race bearing faults is then experimentally verified with results from 12 bearings representing varying degrees of fault severity
High-Speed Architecture Design of Tomlinson&#x2013;Harashima Precoders (2007)

Like decision feedback equalizers (DFEs), Tomlinson-Harashima precoders (TH precoders) contain nonlinear feedback loops, which limit their use for high-speed applications. Unlike in DFEs where the output levels of the nonlinear devices are finite, in TH precoders, theoretically, the output levels of the modulo devices are infinite. Thus, it is difficult to apply look-ahead and pre-computation techniques to pipeline TH precoders, which were successfully applied to pipeline infinite-impulse response (IIR) filters and DFEs in the past. In this paper, three approaches are proposed to design high-speed TH precoders. In the first approach, the traditional block processing technique for DFEs is generalized to the design of high-speed TH precoders. In the second approach, based on the equivalent form of a TH precoder where the precoder can be viewed as an IIR filter with an input equal to the sum of the original input to the TH precoder and a finite-level compensation signal, two high-speed pipelined designs are developed. In the third approach, parallel processing techniques for fast IIR filters are generalized to the design of parallel TH precoders.
Pump beam combiner based on single mode fibres (2009)

Cladding pumped fibre lasers have been rapidly researched and developed with help of semiconductor laser diode bar and stack [1]. Especially these fiber lasers showed a high power conversion efficiency of about ∼80% in case of Yb-doped double clad fiber laser and a high-quality beam of M <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> ≈ 1. Output power of a fiber laser is determined by how much a pump light can be intensely coupled into an inner cladding layer of a double clad fiber. In this paper, we introduce an efficient pump beam combiner based on single mode fibres.
An Efficient Method Based on the Electromagnetic Time Reversal to Locate Faults in Power Networks (2013)

This paper presents a new method based on the electromagnetic time-reversal (EMTR) theory for locating faults in power networks. The applicability of the EMTR technique to locate faults is first discussed. Using the classical transmission-line equations in the frequency domain, analytical expressions are derived to infer the location of the fault. The accuracy of the proposed method is then discussed in relation to the number of observation points adopted to record the fault-originated electromagnetic transients. Then, this paper illustrates the extension of the proposed method to the time domain. The experimental validation of the proposed method is presented by making reference to a reduced-scale coaxial cable system where real faults are hardware-emulated. Finally, the application of the proposed EMTR-based fault-location method to Electromagnetic Transients Program-simulated cases is presented. The simulated test cases are: a mixed overhead/coaxial cable transmission system and the IEEE 34-bus distribution test feeder. Compared to other transient-based fault-location techniques, the proposed method presents a number of advantages, namely, its straightforward applicability to inhomogeneous media (mixed overhead and coaxial power cable lines), the use of a single observation (measurement) point, and robustness against fault type and fault impedance.
New 2-Alkylidene 1α,25-Dihydroxy-19-norvitamin D<sub>3</sub> Analogues of High Intestinal Activity:  Synthesis and Biological Evaluation of 2-(3‘-Alkoxypropylidene) and 2-(3‘-Hydroxypropylidene) Derivatives (2006)

In a search for novel vitamin D compounds of potential therapeutic value, E- and Z-isomers of 1alpha,25-dihydroxy-2-(3'-hydroxypropylidene)-19-norvitamin D(3), as well as a derivative of the former compound possessing a 3'-(methoxymethoxy)propylidene substituent at C-2, were efficiently prepared. All vitamins were obtained in convergent syntheses, starting with (-)-quinic acid and the protected 25-hydroxy Grundmann ketones. Quinic acid was converted into keto lactone 11, and a substituted hydroxypropylidene group was attached by Wittig reaction yielding pairs of isomeric compounds 12, 13 and 14, 15. These olefinic products were then transformed into phosphine oxides 32-34 which were subjected to Lythgoe type Wittig-Horner coupling with C,D-fragments 35a and 35b. An alternative route was also elaborated that comprised Julia coupling of sulfones 39a and 39b with the cyclohexanone derivative 23. The binding of all synthesized vitamins to the full-length rat recombinant vitamin D receptor (VDR) is either similar to or within one log of 1alpha,25(OH)(2)D(3). The in vivo tests have revealed that the calcemic activity of all analogues in the E-series (5a, 6a, 6b) is considerably higher than that of the native hormone.
Performance characteristics of a continuous-wave compact widely tunable external cavity interband cascade lasers (2010)

We present the design and performance of a novel broadly tunable continuous-wave external-cavity interband cascade laser (ECicL). The ICL die growth and fabrication, as well as the external cavity geometry are described. Tuning across the 3.2-3.35 microm wavelength range, limited by the gain width of the ICL active medium, is achieved at a maximum power level of 4 mW.
Extracellular Antibody Drug Conjugates Exploiting the Proximity of Two Proteins (2016)

The human Na<sup>+</sup>/K<sup>+</sup>-ATPase (NKA) is a plasma membrane ion pump that uses ATP to help maintain the resting potential of all human cells. Inhibition of the NKA leads to cell swelling and death. The results of this investigation show that on cancer cells, the NKA either comes in close proximity to, associate with or complexes to important cancer-related proteins, and thus can be targeted with a new type of precision therapy called the extracellular drug conjugate or EDC. The EDCs reported here exhibit EC<sub>50</sub> values in the low to mid-picomolar range, and signal to noise ratios > 1,000:1, both of which are dependent on the cell surface expression of the NKA and corresponding cancer-related target. We demonstrate that a potent small molecule inhibitor of the NKA can be covalently attached to antibodies targeting CD20, CD38, CD56, CD147, or dysadherin, to create a series of selective and powerful EDCs that kill cancer cells extracellularly by a mechanism resembling necrosis. This is therefore a framework for the development of a new type of precision therapy wherein exquisite selectivity is achieved for targeting extracellular disease-related proteins.
Nanostructured thin films produced in flame aerosol reactors for photosplitting of water (2006)

The paper describes methodologies for deposition of nanostructured films in single step processes using flame aerosol reactors. An understanding of the process parameters such as precursor feed rate, temperature histories and residence times that control resultant film parameters such as thickness, crystallinity and morphology are developed. Control of temperature profiles allow control of sintering rates to produce desired nanostructured thin films. These films are then tested for photocurrent generation under uv light illumination - and overall conversion efficiencies of around 5 % are readily obtained. Results of the study indicate that conditions could be optimized to improve water splitting efficiencies.
Organic light emitting devices with enhanced operational stability at elevated temperatures (2002)

Temperature dependence of electroluminescence degradation is studied in organic light emitting devices containing an emitting layer composed of a mixture of N,N′-di(naphthalene-1-yl)-N,N′-diphenyl-benzidine and tris(8-hydroxyquinoline)aluminum (AlQ3), doped with quinacridone green emitter. The emitting layer is sandwiched between hole and electron transport layers. Electroluminescence degradation in time is measured on devices operated at temperatures ranging from 22 to 100 °C. The devices demonstrated remarkable stability, even at elevated temperatures. From accelerated degradation tests, a device half-life of about 78 500, 18 700, and 8600 h can be projected for devices operated at 22, 70, and 100 °C, respectively, at an initial device luminance of 100 cd/m2. Activation energy for device degradation of 0.27 eV is consistent with the recently proposed degradation mechanism based on the unstable cationic AlQ3 species.