gebhart/patrepeval huggingface dataset:
Spherical Nucleic Acid Nanoparticle Conjugates as an RNAi-Based Therapy for Glioblastoma* (2020)

Glioblastoma multiforme (GBM) is a neurologically debilitating disease that culminates in death 14 to 16 months after diagnosis.An incomplete understanding of how cataloged genetic aberrations promote therapy resistance, combined with ineffective drug delivery to the central nervous system, has rendered GBM incurable.Functional genomics efforts have implicated several oncogenes in GBM pathogenesis but have rarely led to the implementation of targeted therapies.This is partly because many "undruggable" oncogenes cannot be targeted by small molecules or antibodies.We preclinically evaluate an RNA interference (RNAi)-based nanomedicine platform, based on spherical nucleic acid (SNA) nanoparticle conjugates, to neutralize oncogene expression in GBM.SNAs consist of gold nanoparticles covalently functionalized with densely packed, highly oriented small interfering RNA duplexes.In the absence of auxiliary transfection strategies or chemical modifications, SNAs efficiently entered primary and transformed glial cells in vitro.In vivo, the SNAs penetrated the blood-brain barrier and blood-tumor barrier to disseminate throughout xenogeneic glioma explants.SNAs targeting the oncoprotein Bcl2Like12 (Bcl2L12)-an effector caspase and p53 inhibitor overexpressed in GBM relative to normal brain and low-grade astrocytomas-were effective in knocking down endogenous Bcl2L12 mRNA and protein levels, and sensitized glioma cells toward therapyinduced apoptosis by enhancing effector caspase and p53 activity.Further, systemically delivered SNAs reduced Bcl2L12 expression in intracerebral GBM, increased intratumoral apoptosis, and reduced tumor burden and progression in xenografted mice, without adverse side effects.Thus, silencing antiapoptotic signaling using SNAs represents a new approach for systemic RNAi therapy for GBM and possibly other lethal malignancies.
Prostate elastography: preliminary in vivo results (2005)

We report preliminary results from our investigation of in vivo prostate elastography. Fewer than 50% of all prostate cancers are typically visible in current clinical imaging modalities. Elastography displays a map of strain that results when tissue is externally compressed. Thus, elastography is ideal for imaging prostate cancers because they are generally stiffer than the surrounding tissue and stiffer regions usually exhibit lower strain in elastograms. In our study, digital radio-frequency (RF) ultrasound echo data were acquired from prostate-cancer patients undergoing brachytherapy. Seed placement is guided by a transrectal ultrasound (TRUS) probe, which is held in a mechanical fixture. The probe can be moved in XYZ directions and tilted. The probe face, in contact with the rectal wall, is used to apply a compression force to the immediately adjacent prostate. We also used a water-filled (acoustic) coupling balloon to compress the prostate by increasing the water volume inside the balloon. In each scan plane (transverse), we acquired RF data from successive scans at the scanner frame rate as the deformation force on the rectal wall was continuously increased. We computed strain using 1D RF cross-correlation analysis. The compression method based on fixture displacement produced low-noise elastograms that beautifully displayed the prostate architecture and emphasized stiff areas. Balloon-based compression also produced low-noise elastograms. Initial results demonstrate that elastography may be useful in the detection and evaluation of prostate cancers, occult in conventional imaging modalities.
The Impact of Bottom Electrode Coverage Rate on Electromechanical Coupling and Quality Factor of AlN MEMS Contour Mode Resonators (2019)

This paper reports the impact of bottom electrode design on electromechanical coupling (k <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> t) and quality factor (Q) of laterally vibrating aluminum nitride (AlN) contour-mode resonators (CMRs). AlN-CMRs with various bottom electrode coverage rates ranging from 33% to 120% are fabricated at two different center frequencies of 220 MHz and 1 GHz. We have measured a total of 160 devices and the results show that bottom electrode coverage rate clearly affects both and Q, inducing shifts as much as 230% and 890%, respectively. The changes in aforementioned properties are different for the tested center frequencies. It has shown that the bottom coverage rate determines the active (or vibrating) region of the resonator, and thus directly impacting Q. In contrast, k <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> increases with the bottom coverage rate, regardless to the center frequency of the resonator. Our findings indicate that a careful selection of the bottom electrode design could optimize or even improve both k <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">t</sub> <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> and Q, which ultimately determines the power budget and noise level of AlN MEMS resonators.
Adaptive control of a production-inventory system (1981)

We study a production-inventory system in which input is deterministic, and its rate is the controlled parameter. The output is a compound Poisson process with exponential jump-size distribution. The parameters of the output process are unknown. The following adaptive policy is used: At each time t the unknown parameters are estimated by maximum likelihood method and the input rate which would be optimal if these were the true values of the parameter is used. The issues investigated are (1) the convergence of maximum likelihood estimates to the true value, and (2) the asymptotic properties of the cost under the adaptive policy.
Oxygen Switch in Visible-Light Photoredox Catalysis: Radical Additions and Cyclizations and Unexpected C–C-Bond Cleavage Reactions (2013)

Visible light photoredox catalyzed inter- and intramolecular C-H functionalization reactions of tertiary amines have been developed. Oxygen was found to act as chemical switch to trigger two different reaction pathways and to obtain two different types of products from the same starting material. In the absence of oxygen, the intermolecular addition of N,N-dimethyl-anilines to electron-deficient alkenes provided γ-amino nitriles in good to high yields. In the presence of oxygen, a radical addition/cyclization reaction occurred which resulted in the formation of tetrahydroquinoline derivatives in good yields under mild reaction conditions. The intramolecular version of the radical addition led to the unexpected formation of indole-3-carboxaldehyde derivatives. Mechanistic investigations of this reaction cascade uncovered a new photoredox catalyzed C-C bond cleavage reaction.
ChemInform Abstract: Nanocrystalline Gold and Gold Palladium Alloy Catalysts for Chemical Synthesis (2008)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Reflectarray design based on interdigital gap loading element (2010)

In this paper, a broad angle reflectarray is designed which can scatter the normal incident wave to a large angle (up to 60°) from the normal direction of the planar reflectarray to eliminate the blind areas of the base station in wireless communication scenarios. In our research, a novel individual element which is composed of a dipole with interdigital gap structure printed on a single-layer substrate is used to construct the reflectarray. Only one degree of freedom is introduced to extend the phase range of the unit cell to more than 1000°. Furthermore, a reflectarray with a large scattering angle is designed to eliminate blind spots in communication between the base station and mobile users.
Synthesis and Structure–Activity Relationships of DCLK1 Kinase Inhibitors Based on a 5,11-Dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one Scaffold (2020)

Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that is overexpressed in gastrointestinal cancers, including esophageal, gastric, colorectal, and pancreatic cancers. DCLK1 is also used as a marker of tuft cells, which regulate type II immunity in the gut. However, the substrates and functions of DCLK1 are understudied. We recently described the first selective DCLK1/2 inhibitor, DCLK1-IN-1, developed to aid the functional characterization of this important kinase. Here we describe the synthesis and structure-activity relationships of 5,11-dihydro-6<i>H</i>-benzo[<i>e</i>]pyrimido[5,4-<i>b</i>][1,4]diazepin-6-one DCLK1 inhibitors, resulting in the identification of DCLK1-IN-1.
Chip-level MMSE equalization in the forward link of UMTS-FDD: a low complexity approach (2003)

Equalization in the forward link of code division multiple access (CDMA) channels has been proposed as an alternative to the RAKE receiver. If the spreading codes are orthogonal (as in UMTS-FDD) and the channel is frequency-flat, the RAKE receiver is optimal. However, frequency-selective fading channels destroy the orthogonality of the spreading codes and chip level equalization is needed in order to restore the orthogonality. We show that the permanent code-multiplexed pilot channel of UMTS-FDD can be used to provide a consistent estimate of the MMSE equalizer. We discuss a low complexity adaptive algorithm that could be used for equalization, namely the stochastic gradient multi-stage Wiener filter (SG-MSWF), which is a sample-by-sample version of the MSWF. Simulations are carried out in a time-varying frequency-selective fading environment and show that the proposed algorithm can achieve performances that are close to those of the optimal with a substantial gain in complexity.
Detection of Minimal Disease in Bone Marrow of Neuroblastoma Patients by Immunofluorescence (1989)

Indirect immunofluorescence studies were compared with conventional smear cytology in 82 paired bone marrow samples from children with neuroblastoma using monoclonal antibodies (MAbs) BW 575 (neuroblastoma-associated 95 kD glycoprotein) and BW 625 (ganglioside GD2) and tetanus toxin labeling. Congruent results were obtained in 70 of 82, or 85% (positive/positive; negative/negative). In 12 of 82 (15%) patients, bone marrow infiltration was demonstrated by immunofluorescence but not by conventional cytology. As few as 0.01% neuroblastoma cells were reliably detected--in some cases even fewer. Because of antigen heterogeneity, false negative results were obtained in five cases with MAb BW 625, in two cases with MAb BW 575, and in no case with tetanus toxin. No antibodies showed any cross-reactivity to hematopoietic cells in either bone marrow of infants or during regeneration after chemotherapy. We conclude that this panel of antibodies is highly sensitive and specific to detect minimal disease in bone marrow of neuroblastoma patients, which has major implications for the staging procedure, monitoring treatment, early detection of relapse, and assessment of bone marrow status before autologous bone marrow transplantation.
DIAGNOSTICS OF REINFORCED CONCRETE BRIDGES BY ACOUSTIC EMISSION (2002)

Our work on concrete bridges will be reported. We found that AE is the most suitable method for the purpose of old bridge inspection and further development effort was conducted. This culminated in a draft document, “Recommended Practice for Testing Reinforced and Pre-stressed Concrete Structures by Acoustic Emission ” (RP), following the lead of documents of a similar nature in Japan and in Texas. We will report here selectively the test results of five full-scale bridges following the procedures we have proposed. These bridges were of different types of construction: reinforced concrete, pre-stressed concrete (post-tensioned and pre-tensioned) and combined concrete-steel construction. These justified the basic principles of RP, but also demonstrated needs of individual modification fitting the structures and testing conditions.
Discovery and preclinical development of vismodegib (2014)

The authors' experience in target-based drug discovery suggests that vismodegib's path to the clinic deserves some reflection to identify key steps that have contributed to its success. Targeting the Hh pathway with vismodegib blocks the abberant signaling caused by mutational inactivation of the negative regulator PTCH1 or mutational activation of SMO. Vismodegib gives physicians a treatment option for patients with locally advanced or metastatic BCC for whom surgery or radiation is not recommended.
Introduction to Therm Net Technology (1998)

Abstract The Introduction to Therm Net technology is an overview of how radio frequency (RF) beating can be implemented to enhance conventional remediation technologies. Included in the article is a case study of a project conducted in March 1996 at a gasoline release site. The project consisted of a “hot spot” application to reduce BETX concentrations to achieve site closure. The application consisted of RF heating, soil vapor extraction, and groundwater ventilation. A bench scale study was also conducted to measure the effects that RF heating and vapor extraction had on the removal of PAH constitutents from a coal tar sludge. Up to 100 percent reductions were observed for some of the constituents in the study. Also included is a graphical representation of temperature versus vapor pressure for contaminants typically encountered at remediation sites, illustrating that as temperature increases, the removal rate increases.
Effect of Cefazolin and Vancomycin on Osteoblasts In Vitro (1996)

The effect of cefazolin and vancomycin on osteoblast-like cells was studied. Cells from the MG-63 human osteosarcoma cell line were grown in antibiotic free media and exposed to concentrations of cefazolin and vancomycin at order of magnitude intervals between 0 and 10,000 microg/ml. For cefazolin, a second interval was performed between 100 and 1000 microg/ml to define toxic levels more accurately. Cell number and 3H-thymidine incorporation at 0, 24, and 72 hours were determined. The results of this study show that local levels of vancomycin of 1000 microg/ml and less have little or no effect on osteoblast replication, and concentrations of 10,000 microg/ml cause cell death. Concentrations of cefazolin of 100 microg/ml and less have little or no effect on osteoblast replication, 200 microg/ml significantly decrease cell replication, and 10,000 microg/ml cause cell death. The authors conclude that vancomycin is less toxic than is cefazolin to osteoblasts at higher concentrations and may be a better antibiotic for local administration in the treatment of similarly sensitive bacterial infections.
Data from Comprehensive Genome Methylation Analysis in Bladder Cancer: Identification and Validation of Novel Methylated Genes and Application of These as Urinary Tumor Markers (2023)

&lt;div&gt;Abstract&lt;p&gt;&lt;b&gt;Purpose:&lt;/b&gt; Epigenetic alterations are common and can now be addressed in a parallel fashion. We investigated the methylation in bladder cancer with respect to location in genome, consistency, variation in metachronous tumors, impact on transcripts, chromosomal location, and usefulness as urinary markers.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; A microarray assay was utilized to analyze methylation in 56 samples. Independent validation was conducted in 63 samples by a PCR-based method and bisulfite sequencing. The methylation levels in 174 urine specimens were quantified. Transcript levels were analyzed using expression microarrays and pathways were analyzed using dedicated software.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Results:&lt;/b&gt; Global methylation patterns were established within and outside CpG islands. We validated methylation of the eight tumor markers genes &lt;i&gt;ZNF154&lt;/i&gt; (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), &lt;i&gt;HOXA9&lt;/i&gt; (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), &lt;i&gt;POU4F2&lt;/i&gt; (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), &lt;i&gt;EOMES&lt;/i&gt; (&lt;i&gt;P&lt;/i&gt; = 0.0005), &lt;i&gt;ACOT11&lt;/i&gt; (&lt;i&gt;P&lt;/i&gt; = 0.0001), &lt;i&gt;PCDHGA12&lt;/i&gt; (&lt;i&gt;P&lt;/i&gt; = 0.0001), &lt;i&gt;CA3&lt;/i&gt; (&lt;i&gt;P&lt;/i&gt; = 0.0002), and &lt;i&gt;PTGDR&lt;/i&gt; (&lt;i&gt;P&lt;/i&gt; = 0.0110), the candidate marker of disease progression &lt;i&gt;TBX4&lt;/i&gt; (&lt;i&gt;P&lt;/i&gt; &lt; 0.04), and other genes with stage-specific methylation. The methylation of metachronous tumors was stable and targeted to certain pathways. The correlation to expression was not stringent. Chromosome 21 showed most differential methylation (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001) and specifically hypomethylation of keratins, which together with keratin-like proteins were epigenetically regulated. In DNA from voided urine, we detected differential methylation of ZNF154 (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), POU4F2 (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), HOXA9 (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), and EOMES (&lt;i&gt;P&lt;/i&gt; &lt; 0.0001), achieving 84% sensitivity and 96% specificity.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Conclusions:&lt;/b&gt; We initiated a detailed mapping of the methylome in metachronous bladder cancer. Novel genes with tumor, chromosome, as well as pathway-specific differential methylation in bladder cancer were identified. The methylated genes were promising cancer markers for early detection of bladder cancer. &lt;i&gt;Clin Cancer Res; 17(17); 5582–92. ©2011 AACR&lt;/i&gt;.&lt;/p&gt;&lt;/div&gt;
Quantitative Assessment of Fat Levels inCaenorhabditis elegansUsing Dark Field Microscopy (2017)

The roundworm <i>Caenorhabditis elegans</i> is widely used as a model for studying conserved pathways for fat storage, aging, and metabolism. The most broadly used methods for imaging fat in <i>C. elegans</i> require fixing and staining the animal. Here, we show that dark field images acquired through an ordinary light microscope can be used to estimate fat levels in worms. We define a metric based on the amount of light scattered per area, and show that this light scattering metric is strongly correlated with worm fat levels as measured by Oil Red O (ORO) staining across a wide variety of genetic backgrounds and feeding conditions. Dark field imaging requires no exogenous agents or chemical fixation, making it compatible with live worm imaging. Using our method, we track fat storage with high temporal resolution in developing larvae, and show that fat storage in the intestine increases in at least one burst during development.
HiSIM: a MOSFET model for circuit simulation connecting circuit performance with technology (2003)

Circuit simulation models should be pragmatic, but should be accurate at the same time. HiSIM (Hiroshima-University STARC IGFET Model), aiming to fulfil both requirements, is based on an iterative surface-potential determination in 2D device simulators. However, the essence of each technology is extracted from measurements, thus simplifying modeling procedure and allowing large-scale circuit simulation with 0.1 /spl mu/m-MOSFET technologies.
Recombinant Human Tumor Necrosis Factor Enhances Radiosensitivity and Improves Animal Survival in Murine Neuroblastoma (1992)

An analysis of the potential of recombinant human tumor necrosis factor to enhance the radiosensitivity of C1300 murine neuroblastoma was undertaken. Female A/J mice bearing C1300 murine neuroblastoma (right hindlimb) underwent the following treatments: group 1-0.25 cc normal saline intraperitoneally times 2, group 2-0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2, group 3-400 cGy. right hindlimb, group 4-800 cGy. right hindlimb, group 5-400 cGy. right hindlimb plus 0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2 and group 6-800 cGy. right hindlimb plus 0.5 mcg./gm. recombinant human tumor necrosis factor intraperitoneally times 2. All animals were followed for 21 days after treatment initiation with interval measurements of tumor volume. All single modality treatments were more effective than normal saline in reducing average tumor volumes during the study period (800 cGy. equals recombinant human tumor necrosis factor greater than 400 cGy. greater than normal saline). The addition of recombinant human tumor necrosis factor to radiotherapy moderately augmented antitumor response at radiation doses of 400 cGy. but marked enhancement was attained at radiation doses of 800 cGy. (p less than 0.02). This enhancement was achieved without increased animal morbidity or mortality. Animals receiving recombinant human tumor necrosis factor in addition to 800 cGy. demonstrated increased survival when compared with animals receiving 800 cGy. alone (p less than 0.02). Although statistical synergy was not proved, recombinant human tumor necrosis factor appears to augment significantly radiation-induced tumor regression at no toxic cost to the animal.
Ovarian Hormone Deficiency Reduces Intrinsic Excitability and Abolishes Acute Estrogen Sensitivity in Hippocampal CA1 Pyramidal Neurons (2011)

Premature and uncompensated loss of ovarian hormones following ovariectomy (OVX) elevates the risks of cognitive impairment and dementia. These risks are prevented with estrogen (E(2))-containing hormone replacement therapy initiated shortly following OVX but not after substantial delay. Currently, the cellular bases underlying these clinical findings are unknown. At the cellular level, intrinsic membrane properties regulate the efficiency of synaptic inputs to initiate output action potentials (APs), thereby affecting neuronal communication, hence cognitive processing. This study tested the hypothesis that in CA1 pyramidal neurons, intrinsic membrane properties and their acute regulation by E(2) require ovarian hormones for maintenance. Whole-cell current-clamp recordings were performed on neurons from ∼ 7-month-old OVX rats that experienced either short-term (10 d, control OVX) or long-term (5 months, OVX(LT)) ovarian hormone deficiency. The results reveal that long-term hormone deficiency reduced intrinsic membrane excitability (IE) as measured by the number of evoked APs and firing duration for a given current injection. This was accompanied by AP broadening, an increased slow afterhyperpolarization (sAHP), and faster accumulation of Na(V) channel inactivation during repetitive firing. In the control OVX neurons, E(2) acutely increased IE and reduced the sAHP. In contrast, acute regulation of IE by E(2) was absent in the OVX(LT) neurons. Since the degree of IE of hippocampal pyramidal neurons is positively related with hippocampus-dependent learning ability, and modulation of IE is observed following successful learning, these findings provide a framework for understanding hormone deficiency-related cognitive impairment and the critical window for therapy initiation.
Ultra-compact integrated electrical and optical silicone probe for recording and illumination in vivo (2015)

status: Published