gebhart/patrepeval huggingface dataset:
Repeat dose study of the novel proapoptotic chemotherapeutic agent alpha-tocopheryloxy acetic acid in mice (2011)

Alpha-tocopheryloxy acetic acid (α-TEA) is an ether derivative of vitamin E and has been shown to suppress tumor growth in various murine and human xenograft tumor models, including melanoma, breast, lung, prostate, and ovarian cancers. The purpose of this study was to assess its safety and pharmacokinetics after repeat dosing in a preclinical murine model. Male and female mice received α-TEA doses of 100, 300, or 1500 mg/kg/day by daily oral gavage for 28 days. α-TEA serum levels were determined weekly by high-performance liquid chromatography with mass spectrometric detection. After 28 days of dosing, complete blood counts were taken, blood chemistry was analyzed, and histology was performed. Pharmacokinetic parameters were determined after single dosing. There was no mortality, and we found no clinical signs of toxicity in any of the α-TEA doses tested. Histopathological evaluation of major organs (heart, lung, kidney, liver, spleen, jejunum, ileum, and cecum) revealed no significant α-TEA treatment-related lesions. Blood counts revealed low-grade anemia but no other significant differences between treatment and control groups. Blood chemistry revealed moderate liver toxicity that was dose dependent and was absent in the lowest dose group. There were no significant sex-specific differences in the toxicity profile. The half-life of orally administered α-TEA was determined to be 52 h. This is the first report comprehensively evaluating the toxicity profile of this novel anticancer drug and will facilitate the design of clinical trials to evaluate the safety and antitumor efficacy of α-TEA in patients with cancer.
Optimal Filtering to Improve Performance in Hard Disk Drives: Experimental Results (2000)

Abstract Both minimum and nonminimum phase resonances can be found in the model of a hard disk drive actuator. The mechanism has been designed so that most of the resonant frequencies reside above the Nyquist rate of the sampled data control system. These resonances are often not excited until the demands for better system performance require a higher bandwidth controller. But once these resonances are excited, it is important to understand how these resonances alias in the discrete time control system so that effective compensation algorithms can be developed. The purpose of this paper is to demonstrate how nonminimum phase resonances alias in a sampled data control system and to design an optimal filtering algorithm that reduces their effect on the overall system performance. This paper will address these issues and demonstrate how resonances can be overcome which can eventually lead to improved hard disk drive performance.
New photoluminescence defect at 1.0192 eV in silicon molecular beam epitaxy layers ascribed to Cu (1987)

We report a new photoluminescence defect spectrum with a no-phonon transition at 1.0192 eV which emerges in many silicon layers grown on silicon substrates by molecular beam epitaxy. Comparison of the no-phonon transition and the chief local mode (ℏω=7.5 meV) to the well-established Cu-related spectrum at 1.0145 eV suggests that the new defect incorporates Cu as well. Deep level transient measurements support the presence of Cu in the epilayers. We suggest that this defect spectrum has recently been observed by others but was not identified and associated with Cu.
Differential encoding in prefrontal cortex projection neuron classes across cognitive tasks (2020)

SUMMARY Single-cell transcriptomics has been widely applied to classify neurons in the mammalian brain, while systems neuroscience has historically analyzed the encoding properties of cortical neurons without considering cell types. Here we examine how specific transcriptomic types of mouse prefrontal cortex (PFC) projection neurons relate to axonal projections and encoding properties across multiple cognitive tasks. We found that most types projected to multiple targets, and most targets received projections from multiple types, except PFC→PAG (periaqueductal gray). By comparing Ca 2+ -activity of the molecularly homogeneous PFC→PAG type against two heterogeneous classes in several two-alternative choice tasks in freely-moving mice, we found that all task-related signals assayed were qualitatively present in all examined classes. However, PAG-projecting neurons most potently encoded choice in cued tasks, whereas contralateral PFC-projecting neurons most potently encoded reward context in an uncued task. Thus, task signals are organized redundantly, but with clear quantitative biases across cells of specific molecular-anatomical characteristics.
Tungsten plug-in wiring structure for high density three dimensional devices (1991)

A new plug-in wiring structure (PWS) is proposed for higher packing density three dimensional (3D) devices. The PWS features deep via-holes that penetrate active regions of SOI layers, and make contacts at the side of them. The DUAL-CMOS(Dual Active Device Layer CMOS) SRAM cell with the PWS realized 56% cell area of that of bulk-Si CMOS and 70% of that of DUAL-CMOS using conventional wiring structure. The PWS used hydrogen reduction blanket CVD-W film on TiW/Ti or TiW adhesion layer. Via-holes for the PWS and other conventional via-holes were filled by CVD-W simultaneously. When TiW/Ti adhesion layer was used, ohmic side wall contacts to p/sup +/ poly-Si for PWS were formed with specific contact resistance of 50.4 ohms. mu m/sup 2/ for 0.6 mu m phi contacts. Device operation using the PWS was successfully demonstrated with DUAL-CMOS ring oscillators. The propagation delay time was 420 psec/stage, which was approximately 10% faster than DUAL-CMOS ring oscillators without the PWS.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
Load Coupling and Energy Optimization in Multi-Cell and Multi-Carrier NOMA Networks (2019)

In this paper, we investigate energy optimization in multi-cell and multi-carrier non-orthogonal multiple access (NOMA) networks. We apply a load-coupling model for NOMA networks to capture the coupling relation of mutual interference among cells. With this analytical tool, we formulate an energy minimization problem in a NOMA-based load-coupled system, where optimizing load-rate-power allocation, and determining decoding order and user grouping are the key aspects. Theoretically, we prove that the minimum consumed energy can be achieved by using all the time-frequency resources in each cell to deliver users’ demand, and allowing all the users to share resource units. From a practical perspective, we consider three types of NOMA grouping schemes, i.e., all-user grouping, partitioned and non-partitioned grouping. We develop tailored solutions for each grouping scheme to enable efficient load-rate-power optimization. These three algorithmic components are embedded into a power-adjustment framework to provide energy-efficient solutions for NOMA networks. Numerical results demonstrate promising energy-saving gains of NOMA over orthogonal multiple access in large-scale cellular networks, in particular for high-demand and resource-limited scenarios. The results also show fast convergence of the proposed algorithms and demonstrate the effectiveness of the solutions.
Debates on Style of Writing during Southern Dynasties (2011)

Since its independence from the oral speech in ancient China,the written-Chinese style has been playing an increasingly important role in the society.With all the rejection to and suppression of it by traditional forces in feudal China,it turned out one of the major means for grassroots intellectuals to seek their promotion in the social hierarchy.With the prevalence of essay writing and rise of literati during the Southern dynasties(420-589),unprecedented attention was paid to the style of writing,and a lot of essayistic collections were published,thereby making the debates on style of writing an important content of essay-writing studies.Scholars during this period attempted to distinguish the style of writing in terms of bibliography,phonology and literary emotions.Such taxonomies,though incomplete or incomprehensive to some extent,have presented a silhouette of the magnificent literature of the time.
Calcium signaling is gated by a mechanical threshold in three-dimensional environments (2012)

Cells interpret their mechanical environment using diverse signaling pathways that affect complex phenotypes. These pathways often interact with ubiquitous 2(nd)-messengers such as calcium. Understanding mechanically-induced calcium signaling is especially important in fibroblasts, cells that exist in three-dimensional fibrous matrices, sense their mechanical environment, and remodel tissue morphology. Here, we examined calcium signaling in fibroblasts using a minimal-profile, three-dimensional (MP3D) mechanical assay system, and compared responses to those elicited by conventional, two-dimensional magnetic tensile cytometry and substratum stretching. Using the MP3D system, we observed robust mechanically-induced calcium responses that could not be recreated using either two-dimensional technique. Furthermore, we used the MP3D system to identify a critical displacement threshold governing an all-or-nothing mechanically-induced calcium response. We believe these findings significantly increase our understanding of the critical role of calcium signaling in cells in three-dimensional environments with broad implications in development and disease.
A one-step process employing various amphiphiles for an electrically insulating silica coating on graphite (2017)

Herein, we report new way and mechanism to completely coat graphite (3–550 μm) with a silica layer within 12 hours.
Data from PDK1 Attenuation Fails to Prevent Tumor Formation in PTEN-Deficient Transgenic Mouse Models (2023)

&lt;div&gt;Abstract&lt;p&gt;PDK1 activates AKT suggesting that PDK1 inhibition might suppress tumor development. However, while PDK1 has been investigated intensively as an oncology target, selective inhibitors suitable for &lt;i&gt;in vivo&lt;/i&gt; studies have remained elusive. In this study we present the results of &lt;i&gt;in vivo&lt;/i&gt; PDK1 inhibition through a universally applicable RNAi approach for functional drug target validation in oncogenic pathway contexts. This approach, which relies on doxycycline-inducible shRNA expression from the &lt;i&gt;Rosa26&lt;/i&gt; locus, is ideal for functional studies of genes like PDK1 where constitutive mouse models lead to strong developmental phenotypes or embryonic lethality. We achieved more than 90% PDK1 knockdown &lt;i&gt;in vivo&lt;/i&gt;, a level sufficient to impact physiological functions resulting in hyperinsulinemia and hyperglycemia. This phenotype was reversible on PDK1 reexpression. Unexpectedly, long-term PDK1 knockdown revealed a lack of potent antitumor efficacy in 3 different mouse models of PTEN-deficient cancer. Thus, despite efficient PDK1 knockdown, inhibition of the PI3K pathway was marginal suggesting that PDK1 was not a rate limiting factor. &lt;i&gt;Ex vivo&lt;/i&gt; analysis of pharmacological inhibitors revealed that AKT and mTOR inhibitors undergoing clinical development are more effective than PDK1 inhibitors at blocking activated PI3K pathway signaling. Taken together our findings weaken the widely held expectation that PDK1 represents an appealing oncology target. &lt;i&gt;Cancer Res; 71(8); 3052–65. ©2011 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
EvoLUTe: Evaluation of Look-Up-Table-based Fine-Grained IP Redaction (2023)

Recent studies on intellectual property (IP) protection techniques demonstrate that engaging embedded reconfigurable components (e.g., eFPGA redaction) would be a promising approach to concealing the functional and structural information of the security-critical design. However, detailed investigation reveals that such techniques suffer from almost prohibited overhead in terms of area, power, delay, and testability. In this paper, we introduce EvoLUTe, a distinct and significantly more fine-grained redaction methodology using smaller reconfigurable components (such as look-up-tables (LUTs)). In EvoLUTe, we examine both eFPGA-based and LUT-based design spaces, demonstrating that a novel cone-based and fine-grained universal function modeling approach using LUTs is capable of providing the same degree of resiliency at a much lower area/power/delay and testability costs.
Visualization of Tomato Growth Based on Dry Matter Flow (2017)

The visualization of tomato growth can be used in 3D computer games and virtual gardens. Based on the growth theory involving the respiration theory, the photosynthesis, and dry matter partition, a visual system is developed. The tomato growth visual simulation system is light-and-temperature-dependent and shows plausible visual effects in consideration of the continuous growth, texture map, gravity influence, and collision detection. In addition, the virtual tomato plant information, such as the plant height, leaf area index, fruit weight, and dry matter, can be updated and output in real time.
Pervasive speech recognition (2004)

As mobile computing devices grow smaller and as in-car computing platforms become more common, we must augment traditional methods of human-computer interaction. Although speech interfaces have existed for years, the constrained system resources of pervasive devices, such as limited memory and processing capabilities, present new challenges. We provide an overview of embedded automatic speech recognition (ASR) on the pervasive device and discuss its ability to help us develop pervasive applications that meet today's marketplace needs. ASR recognizes spoken words and phrases. State-of-the-art ASR uses a phoneme-based approach for speech modeling: it gives each phoneme (or elementary speech sound) in the language under consideration a statistical representation expressing its acoustic properties.
Tradeoffs and Limits in Computational Imaging (2011)

For centuries, cameras were designed to closely mimic the human visual system. With the rapid increase in computer processing power over the last few decades, researchers in the vision, graphics and optics community have begun to focus their attention on new types of imaging systems that utilize computations as an integral part of the imaging process. Computational cameras optically encode information that is later decoded using signal processing. In this thesis, I show three new computational imaging designs that provide new functionality over conventional cameras. Each design has been rigorously analyzed, built and tested for performance. Each system has demonstrated an increase in functionality over tradition camera designs. The first two computational imaging systems, Diffusion Coding and Spectral Focal Sweep, provide a means to computationally extend the depth of field of an imaging system without sacrificing optical efficiency. These techniques can be used to preserve image detail when photographing scenes that span very large depth ranges. The final example, Gigapixel Computational Imaging, uses a computational approach to overcome limitations in spatial resolution that are caused by geometric aberrations in conventional cameras. While computational techniques can be used to increase optical efficiency, this comes at a cost. The cost incurred is noise amplification caused by the decoding process. Thus, to measure the real utility of a computational approach, we must weigh the benefit of increased optical efficiency against the cost of amplified noise. A complete treatment must take into account an accurate noise model. In some cases, the benefit may not outweigh the cost, and thus a computational approach has no value. This thesis concludes with a discussion on these scenarios.
An organ culture system to model early degenerative changes of the intervertebral disc (2011)

Results of this study show that perturbations in microenvironmental factors result in anatomical and gene expression change within the intervertebral disc that may ultimately compromise cell function and induce pathological deficits. This system would be a valuable screening tool to investigate interventional strategies aimed at restoring disc cell function.
Robust High Speed Position Servo System Considering Current &#x00026; Voltage Limitation and Load Inertia Variation (2007)

A high speed position servo system is important for performance improvement of motion control in several industry applications. It often has the desired position reference. An industrial servo system has the limitation values based on each output of actuator and power amplifier. Hence, a high speed position servo system should keep the tracking control for the desired position reference within the limitation values. Moreover, an industrial servo system must realize the robust control against load torque and load inertia variation. An ordinary position servo system has the complicated control structure caused by the triple minor control loops. On condition of both load inertia variation and the saturation caused by current & voltage limitation, an industrial servo system sometimes has a large overshoot and an oscillated response. Therefore, for the desired quick position reference, it is difficult for a high speed position servo system to keep the robust tracking control against load inertia variation within each limitation of motor current and motor voltage. In order to overcome this problem, this paper proposes a new robust high speed position servo system considering current & voltage limitation and load inertia variation, which is based on disturbance observer. The experimental results confirm that the proposed system realizes the desired & quick & robust response keeping each limitation of speed, current and voltage on condition of both full load torque and three times load inertia variation.
Abstract 3245: Preclinical evaluation of the imipridone family of small molecules, including analogues of clinical-stage anti-cancer small molecule ONC201, reveals potent anti-cancer effects of ONC212 (2017)

Abstract We previously identified a novel, potent anti-cancer small molecule ONC201, which upregulates the integrated stress response (ISR) through ATF4/CHOP/DR5 and acts as a dual inactivator of Akt and ERK, leading to TRAIL gene activation. After completing a first-in-human phase I clinical trial that revealed exceptional safety, therapeutic pharmacokinetic (PK) profile and tumor engagement, ONC201 is under investigation in several advanced cancer Phase I/II trials. Given the unique imipridone core chemical structure of ONC201, we synthesized a family of analogues in an effort to identify additional chemical family members with distinct therapeutic properties. Based on in vitro potency improvements in human cancer cell lines and therapeutic window approximations with normal human fibroblasts, select analogues were investigated in animals for toxicity, maximum tolerated dose (MTD), and antitumor efficacy. ONC212 is one of the most promising new imipridones that was further evaluated to establish the PK profile, oral bioavailability, and efficacy in tumor types that are less sensitive to ONC201. Compared to ONC201, we noted distinct and more rapid kinetics of activity as well as improved potency in multiple human cancer cell lines in vitro. ONC212 has a broad therapeutic window, an acceptable PK profile, and is orally well-tolerated in mice. With no evidence of toxicity at efficacious doses in both colon and triple negative breast cancer, we have begun further evaluation of antitumor efficacy studies in ONC201-resistant tumor types. Efficacy studies with ONC212 are ongoing in melanoma models that are sensitive to ONC212 but less sensitive to ONC201 in vitro. Preliminary data indicates potent tumor growth reduction by ONC212 in vivo in ONC201-resistant melanoma xenografts. With a wide safety margin, potent antitumor activity in ONC201-insenstive tumors, and drug-like characteristics, ONC212 is being further developed as a drug candidate from the new imipridone class of compounds that complements the spectrum of activity of ONC201. Citation Format: Jessica Wagner, C. Leah Kline, Gary Olson, Bhaskara Nallaganchu, Richard Pottorf, Varun Prabhu, Martin Stogniew, Joshua Allen, Wafik El-Deiry. Preclinical evaluation of the imipridone family of small molecules, including analogues of clinical-stage anti-cancer small molecule ONC201, reveals potent anti-cancer effects of ONC212 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3245. doi:10.1158/1538-7445.AM2017-3245
An Analysis of the Binding Function and Structural Organization of the Protein Corona (2020)

Blood proteins adsorb onto the surface of nanoparticles after intravenous injection to form a protein corona. The underlying organization and binding function of these adsorbed proteins remain unclear. This can impact how the corona mediates cell and tissue interactions. Here, we investigated the function and structural organization of the protein corona using an immunoassay approach. We discovered that only 27% of the adsorbed proteins examined are functional for binding to their target protein. This is because the corona architecture is not a monolayer, but an assembly of proteins that are bound to each other. We further demonstrated that we can control the binding functionality of a protein by changing the organization of proteins in the assembly. We show that manipulation of the corona protein composition and assembly can influence their interactions with macrophage cells in culture. This study provides detailed functional and structural insights into the protein corona on nanomaterials and offers a new strategy to manipulate it for controlled interactions with the biological system.
Can Peer Review Be Kinder? Supportive Peer Review: A Re-Commitment to Kindness and a Call to Action (2022)

Peer review aims to select articles for publication and to improve articles before publication. We believe that this process can be infused by kindness without losing rigor. In 2014, the founding editorial team of the <i>Canadian Journal of Kidney Health and Disease</i> (CJKHD) made an explicit commitment to treat authors as we would wish to be treated ourselves. This broader group of authors reaffirms this principle, for which we suggest the terminology "supportive review."
Secreted Metalloprotease Gene Family of Microsporum canis (2002)

Keratinolytic proteases secreted by dermatophytes are likely to be virulence-related factors. Microsporum canis, the main agent of dermatophytosis in dogs and cats, causes a zoonosis that is frequently reported. Using Aspergillus fumigatus metalloprotease genomic sequence (MEP) as a probe, three genes (MEP1, MEP2, and MEP3) were isolated from an M. canis genomic library. They presented a quite-high percentage of identity with both A. fumigatus MEP and Aspergillus oryzae neutral protease I genes. At the amino acid level, they all contained an HEXXH consensus sequence, confirming that these M. canis genes (MEP genes) encode a zinc-containing metalloprotease gene family. Furthermore, MEP3 was found to be the gene encoding a previously isolated M. canis 43.5-kDa keratinolytic metalloprotease, and was successfully expressed as an active recombinant enzyme in Pichia pastoris. Reverse transcriptase nested PCR performed on total RNA extracted from the hair of M. canis-infected guinea pigs showed that at least MEP2 and MEP3 are produced during the infection process. This is the first report describing the isolation of a gene family encoding potential virulence-related factors in dermatophytes.