gebhart/patrepeval huggingface dataset:
Abstract 2265: Expression of hyaluronan in human cancer tissue: A predictive biomarker for PEGPH20-mediated therapy (2010)

Abstract Background: Hyaluronan (HA), a ubiquitous, high-molecular-mass polysaccharide in the precellular and extracellular matrix, is frequently elevated in malignancy, and associated with aggressive disease. Interaction of HA and tumor cells may activate receptor tyrosine kinases, enhance drug resistance, and facilitate tumor progression. A pegylated recombinant human PH20 hyaluronidase (PEGPH20) has been developed to systemically target tumors that accumulated with HA. Systemic PEGPH20 administration in mice bearing PC3 tumors induced a decrease in tumor interstitial fluid pressure (IFP), a decrease in tumor water content, and an increase in tumor vascular volume by enzymatically depleting the HA from the extracellular tumor microenvironment and resulted in significant tumor growth inhibition. PEGPH20 therefore represents an innovative potential treatment approach that may provide improved therapeutic outcomes for cancer patients. Methods: The present study investigated the expression of HA in paraffin embedded human tissue from 9 tumor types as well as corresponding normal tissue by immunohistochemical staining of BioMax tissue arrays with biotinylated HA binding protein (HABP) as a probe. Staining intensity was quantified using Aperio Spectrum plus software. The correlation between HA expression and PEGPH20 response has also been explored using established preclinical models. Results: Strong HA expression was found in 87% of pancreatic, 64% of breast, 50% of multiple myeloma, 46% of NSCLC, 39% of gastric, and 22% of prostate cancer tissues, when compared with corresponding normal tissue (p&amp;lt;0.05). BxPc3 (HA high), MIA PaCa-2 (HA low) and AsPC-1 (HAlow) pancreatic tumor xenografts were evaluated for tumor growth inhibition (TGI) after systemic PEGPH20 treatment and TGI's of 25%, 9% and 15% were observed respectively. In addition, 3 prostate cancers, PC3 (HA high), MatLylu (HA high) and Du145 (HA low) were also evaluated in xenografts with significant growth inhibition shown for PC3 (72%) and MatLylu (34%). Systemic PEGPH20 treatment also induced tumor growth inhibition (60%) for 4T1 (HA high) breast cancer. Conclusion: Accumulation of HA compared to normal tissue was commonly observed and most frequent in pancreatic adenocarcinomas (87%). Furthermore, accumulation of HA was shown to predict response to PEGPH20 therapy in xenograft models (R2=0.805, p&amp;lt;0.01). This work provides strong rationale for exploring efficacy of PEGPH20 in clinical trials. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2265.
Multimodal Characterization of the Late Effects of Traumatic Brain Injury: A Methodological Overview of the Late Effects of Traumatic Brain Injury Project (2018)

Epidemiological studies suggest that a single moderate-to-severe traumatic brain injury (TBI) is associated with an increased risk of neurodegenerative disease, including Alzheimer's disease (AD) and Parkinson's disease (PD). Histopathological studies describe complex neurodegenerative pathologies in individuals exposed to single moderate-to-severe TBI or repetitive mild TBI, including chronic traumatic encephalopathy (CTE). However, the clinicopathological links between TBI and post-traumatic neurodegenerative diseases such as AD, PD, and CTE remain poorly understood. Here, we describe the methodology of the Late Effects of TBI (LETBI) study, whose goals are to characterize chronic post-traumatic neuropathology and to identify in vivo biomarkers of post-traumatic neurodegeneration. LETBI participants undergo extensive clinical evaluation using National Institutes of Health TBI Common Data Elements, proteomic and genomic analysis, structural and functional magnetic resonance imaging (MRI), and prospective consent for brain donation. Selected brain specimens undergo ultra-high resolution ex vivo MRI and histopathological evaluation including whole-mount analysis. Co-registration of ex vivo and in vivo MRI data enables identification of ex vivo lesions that were present during life. In vivo signatures of postmortem pathology are then correlated with cognitive and behavioral data to characterize the clinical phenotype(s) associated with pathological brain lesions. We illustrate the study methods and demonstrate proof of concept for this approach by reporting results from the first LETBI participant, who despite the presence of multiple in vivo and ex vivo pathoanatomic lesions had normal cognition and was functionally independent until her mid-80s. The LETBI project represents a multidisciplinary effort to characterize post-traumatic neuropathology and identify in vivo signatures of postmortem pathology in a prospective study.
Simultaneous pancreas and kidney transplantation: a feasible procedure in selected patients. (1992)

We analyzed the overall results of 24 simultaneous pancreas and kidney transplantations (SPK), performed in our hospital between April 1986 and June 1990. All patients had type I diabetes mellitus and end-stage renal failure. We used bladder drainage of the pancreatic exocrine secretions through a duodenocystostomy. The blood vessels of both grafts were anastomosed to the iliac vessels. The immunosuppressive management was triple-therapy with cyclosporin, azathioprine and prednisone. All organs were transplanted without matching donors and recipients for HLA. At the time of transplantation, mean recipient age was 37 yr; the average duration of diabetes was 22 yr. After disappointing results in the first 4 patients, the pancreas was placed intraperitoneally instead of extraperitoneally and the antibiotic drug regimen was altered. In the second group (n = 20), patient survival was 100%; 1-yr pancreas and kidney graft survival were 65 and 62%, respectively. Duration of hospitalization and pancreas and kidney graft loss were positively correlated with the number of rejection episodes. After 1 yr of follow-up, the mean creatinine clearance was 62 ml/min and the mean HbA1c was 5.5%. Blood glucose levels and oral glucose tolerance tests were also normal. We conclude that patient and graft survival after SPK are satisfactory, although rejection-related morbidity is still a major problem.
3,5,7-Substituted Pyrazolo[4,3-d]Pyrimidine Inhibitors of Cyclin-Dependent Kinases and Cyclin K Degraders (2022)

3,5,7-Trisubstituted pyrazolo[4,3-<i>d</i>]pyrimidines have been identified as potent inhibitors of cyclin-dependent kinases (CDKs), which are established drug targets. Herein, we describe their further structural modifications leading to novel nanomolar inhibitors with strong antiproliferative activity. We determined the crystal structure of fully active CDK2/A2 with 5-(2-amino-1-ethyl)thio-3-cyclobutyl-7-[4-(pyrazol-1-yl)benzyl]amino-1(2)<i>H</i>-pyrazolo[4,3-<i>d</i>]pyrimidine (<b>24</b>) at 1.7 Å resolution, confirming the competitive mode of inhibition. Biochemical and cellular assays in lymphoma cell lines confirmed the expected mechanism of action through dephosphorylation of retinoblastoma protein and RNA polymerase II, leading to induction of apoptosis. Importantly, we also revealed an interesting ability of compound <b>24</b> to induce proteasome-dependent degradation of cyclin K both in vitro and in a patient-derived xenograft in vivo. We propose that <b>24</b> has a dual mechanism of action, acting as a kinase inhibitor and as a molecular glue inducing an interaction between CDK12 and DDB1 that leads to polyubiquitination of cyclin K and its subsequent degradation.
Serological Evidence that Yersinia enterocolitica Lipopolysaccharide produced during Growth in vivo Resembles that Produced during Growth in vitro at 25 C (1983)

Partial smooth-rough transition was observed in 30 strains of Yersinia enterocolitica O:3 cultivated at 37 degrees C. Immunodiffusion and haemagglutination inhibition tests with eight patients' sera demonstrated that the immunogenicity of the lipopolysaccharide of Yersinia enterocolitica in vivo was similar to that of the bacteria grown in vitro at 25 degrees C.
A Polar Code Hybrid Rate Matching Scheme (2018)

In recent 3GPP NR standards discussions for 5G, polar codes have been adopted as the control channel coding scheme when the payload size is more than 11 bits. The rate matching schemes for polar codes include shortening, puncturing and repetition. Each of these rate matching schemes has a performance advantage for different conditions. Hence, it is beneficial to include all three types of rate matching schemes. A circular buffer is also designed to support these rate matching schemes. In this paper, we propose a hybrid rate matching scheme which incorporates both shortening and puncturing techniques. This hybrid rate matching scheme provides a performance advantage for some conditions. Also, this hybrid rate matching scheme does not cause a significant impact on the existing polar coding system architecture. Simulation results are provided to show the performance benefit of this hybrid rate matching scheme.
A novel IP Routing/Signaling based service provisioning concept for ubiquitous grid networking environment (2010)

With the advance of ubiquitous society including IPv6, it is expected that everything will be connected to the networking environment. Then, a ubiquitous grid networking environment (uGrid) has been proposed. In uGrid, everything from a device to a program is defined as “Service-Part”, and new mash-up services can be provided by connecting several ServiceParts. In this paper, IP Routing/Signaling-based uGrid service provisioning is proposed as a new concept for realizing uGrid. The feature of this concept is to assign IP addresses to ServiceParts and execute uGrid service provisioning in the network layer (IP protocol layer). IP protocol is an originally scalable protocol. Also, many sophisticated technologies accumulated for years can be used in IP protocol. Therefore, by using IP protocol, the construction of scalable and intelligent uGrid is expected. As key techniques, Service Routing and Service Signaling are introduced, and the issues of each technique are listed. By experiment, it was confirmed that the provisioning of a simple video grid service was succeeded by Service Signaling.
Bildungsbedingungen von Zinkferriten im Hinblick auf die Entfernung von Schwermetallen aus Abwässern durch Magnetseparation (1996)

Abstract Die Magnetseparation kann zur Entfernung von Schwermetallen aus Abwässern angewandt werden, wenn es gelingt, die Schwermetalle an einen Stoff zu binden, auf den im Magnetfeld eine ausreichend große Kraft wirkt. Ein solcher Feststoff ist der ferrimagnetische Magnetit, der unter bestimmten Bedingungen im Abwasser selbst – durch Oxidation von Eisen(II)‐hydroxid – gebildet werden kann. Für die vorliegenden Arbeiten wurde Zink als Beispiel für großtechnisch relevante, diamagnetische Schwermetalle gewählt. Gegenstand der Untersuchungen war die Frage, welchen Einfluß Zink auf die Struktur und die magnetischen Eigenschaften der Reaktionsprodukte hat, die bei der Oxidation von Eisen(II)‐hydroxid in Gegenwart von Zinkionen in wäßriger Phase bei 25°C gebildet werden. Die Oxidation erfolgte durch Einleiten von synthetischer Luft und konnte kontinuierlich anhand der Änderung von pH‐Wert, Redoxspannung und Sauerstoffkonzentration verfolgt werden. Es ergaben sich typische zeitliche Verläufe der Parameter, die als Maß für den Reaktionsfortschritt verwendet werden können. Die Ergebnisse zeigen, daß Magnetit nur gebildet werden kann, wenn die Ausgangs‐Stoffmengenkonzentration an Eisen(II) größer als die vierfache Konzentration gelösten Sauerstoffs ist und wenn der Sauerstoff langsam – z. B. über einen vorgelagerten Stoffübergang – zugeführt wird. Die Endprodukte, die aus zinkhaltigen Eisen(II)‐Lösungen erhalten wurden, zeigten eine von der Zink‐Ausgangskonzentration abhängige Farbe und stellten ein Gemisch aus Magnetit, Zinkferrit und amorphem Eisen(III)‐hydroxid dar. Dabei war zu beobachten, daß mit steigender Zink‐Ausgangskonzentration zunehmend mehr Zinkferrit, aber auch zunehmend mehr amorphes Eisen(III)‐hydroxid gebildet wird. Das Zink beeinflußt anscheinend die Reaktion derart, daß nicht mehr das thermodynamisch stabile Ferritgitter, sondern ein amorphes Produkt als Gemisch von Eisen(III)‐ und Zinkhydroxid gebildet wird. Auch die magnetischen Eigenschaften zeigten eine Abhängigkeit von der Zinkkonzentration: Die Sättigungsmagnetisierungen stiegen mit abnehmendem Zinkanteil in der Ausgangslösung. Des weiteren zeigte das Reaktionsprodukt bei einem Ausgangsmolverhältnis von Zn: Fe = 1:1 nur noch paramagnetisches Verhalten.
Variable Nitrogen Fixation in Wild Populus (2016)

The microbiome of plants is diverse, and like that of animals, is important for overall health and nutrient acquisition. In legumes and actinorhizal plants, a portion of essential nitrogen (N) is obtained through symbiosis with nodule-inhabiting, N2-fixing microorganisms. However, a variety of non-nodulating plant species can also thrive in natural, low-N settings. Some of these species may rely on endophytes, microorganisms that live within plants, to fix N2 gas into usable forms. Here we report the first direct evidence of N2 fixation in the early successional wild tree, Populus trichocarpa, a non-leguminous tree, from its native riparian habitat. In order to measure N2 fixation, surface-sterilized cuttings of wild poplar were assayed using both 15N2 incorporation and the commonly used acetylene reduction assay. The 15N label was incorporated at high levels in a subset of cuttings, suggesting a high level of N-fixation. Similarly, acetylene was reduced to ethylene in some samples. The microbiota of the cuttings was highly variable, both in numbers of cultured bacteria and in genetic diversity. Our results indicated that associative N2-fixation occurred within wild poplar and that a non-uniformity in the distribution of endophytic bacteria may explain the variability in N-fixation activity. These results point to the need for molecular studies to decipher the required microbial consortia and conditions for effective endophytic N2-fixation in trees.
OVS-DPDK Port Mirroring via NIC Offloading (2020)

As SDN-based networking infrastructure continues to evolve, an increasing number of traditional network functions are deployed over virtualized network. Like traditional networks, traffic monitoring in a Software Defined Network is critical in order to ensure security and performance of the underlying infrastructure. In the context of virtualized networks, deployment of a virtualized TAP service has been reported as an effective VNF that can provide the same monitoring capabilities as a physical TAP. Unfortunately, over a para-virtualization environment, e.g. OVS, where inter-VM communication is expensive it has been observed that virtual TAPs can contribute up to 70% performance degradation. In this paper, we present a hybrid approach that allows network administrators to mirror VIRTIO port traffic to another VF (SR-IOV) via NIC hardware offloading. As a result, the mirrored traffic can be viewed through a monitoring VNF in a separate VM. Through this approach, the throughput overhead can be reduced by as much as 50%.
Cortical, thalamic, and hypothalamic responses to cooling and warming the skin in awake humans: A positron-emission tomography study (2005)

Thermoregulatory mechanisms are remarkably efficient, ensuring minimal temperature variation within the core of the human body under physiological conditions. Diverse afferent and efferent neural pathways contribute to the monitoring of core and skin temperature, generation of heat, and control of thermal exchange with the external environment. We have investigated the cortical, thalamic, and hypothalamic responses to cooling and warming by using positron-emission tomography activation imaging of subjects clad in a water-perfused suit, which enabled rapid change of their skin-surface temperature. Human brain regions that respond to changes in skin temperature have been identified in the somatosensory cortex, insula, anterior cingulate, thalamus, and hypothalamus, with evidence that the hypothalamic response codes for the direction of temperature change. We conclude that signals from thermosensors in the skin providing crucial afferent information to the brain are integrated with signals from central thermosensors, resulting in thermoregulatory responses that maintain core temperature within a remarkably narrow range.
Supplementary figures from Induction of Telomere Dysfunction Prolongs Disease Control of Therapy-Resistant Melanoma (2023)

&lt;p&gt;Supplementary Fig. 1: Related to Fig. 2 (A) The percentage of apoptotic and dead cells indicated as PSVue 643+ cells in each of 12 BRAF-mutant melanoma cell lines treated with PLX4720 or 6-thio-dG at indicated doses for 120 hours. Cells were then harvested and co-stained with PSVue643 and Propidium iodide (PI). The average of 2 biological replicates was plotted. (B) SA-β-gal staining of 4 BRAF-mutant melanoma cell lines treated with 6-thio-dG at 5μM for 9 days. A representative image of 3 biological replicates was shown for each experimental sample. (C and D) Mouse weights of 1205Lu (C) and A375 (D) xenografts in each treatment group were shown. upplementary Fig. 2: Related to Fig. 4 (A) Long-term cell growth assay of 4 melanoma cell lines that acquired resistance to MAPKi treated with 6-thio-dG at indicated doses for 12 days. Cells were then fixed and stained with 3 crystal violet. A representative image of 2 biological replicates was shown for each experimental condition. (B-D) Tumor volumes of WM9 BR (B), UACC-903 BR (C) and A2058 CR (D) xenografts that were treated with the vehicle control and 6-thio-dG at indicated doses. (E) The ssGSEA plot of 11 MSigDB gene sets related to telomere and telomerase that were significantly altered in LOX-IMVI BR cells treated with BIBR 1532 (BIBR) or 6-thio-dG (6dG). (F-I) The heatmaps of RPPA data depicting 30 proteins that were most significantly down-regulated in four representative BR cell lines treated with 6-thio-dG, including A375 BR (F), WM3936-1 (G), 1205Lu BR (H) and WM1552C BR (I). (J) Western blotting of proteins that were downregulated in LOX-IMVI BR cells treated with 6-thio-dG (6dG). (K) The immnohistochemical analysis of AXL was performed in A375 tumors that were treated with the control, 6-thio-dG and Dabrafenib. Supplementary Fig. S3: Related to Fig. 5 (A-C) The heatmaps of two telomere transcriptional gene signatures, two melanoma-specific gene sets and two MAPK pathway-related gene sets in three datasets in which transcriptomes of paired pre- and post-treatment tumor biopsies derived from patients who progressed on MAPKi were profiled. 5 Supplementary Fig. S4: Related to Fig. 5 6 The heatmaps of two telomere transcriptional gene signatures, two melanoma-specific gene sets and two MAPK pathway-related gene sets in paired pre-, on- and post-treatment tumor biopsies derived from 16 patients who were treated with immunotherapies. Supplementary Fig. S5: Related to Fig. 6 (A-E) The heatmaps of RPPA data depicting 30 proteins that were most significantly downregulated in 5 short-term cultures or cell lines derived from immunotherapy-resistant tumors that were treated with 6-thio-dG, including 13-456-3-3 (A), 15-1761-1-2 (B), WM4265-1 (C), WM4265-2 (D) and G43 (E).&lt;/p&gt;
Offshore wave power measurements—A review (2011)

The first wave power patent was filed in 1799. Since then, hundreds of ideas for extraction of energy from ocean waves have surfaced. In the process of developing a concept, it is important to learn from previous successes and failures, and this is not least important when moving into the ocean. In this paper, a review has been made with the purpose of finding wave power projects that have made ocean trials, and that also have reported what has been measured during the trials, and how it has been measured. In relation to how many projects have done work on wave power, surprisingly few have reported on such measurements. There can be many reasons for this, but one is likely the great difficulties in working with experiments in an ocean environment. Many of the projects have reported on sensor failures, unforeseen events, and other general problems in making measurements at sea. The most common site measurement found in this review was wave height. Such measurements was almost universal, although the technologies used differed somewhat. The most common device measurements were electric voltages and/or currents and system pressures (air and water). Device motion and mooring forces were also commonly measured. The motion measurements differed the most between the projects, and many varying methods were used, such as accelerometers, wire sensors, GPS systems, optical systems and echo sounders.
RTS noise reduction of CMOS image sensors using amplifier-selection pixels (2013)

This paper describes a RTS (random telegraph signal) noise reduction technique for an active pixel CMOS image sensor (CIS) with in-pixel selectable dual source-follower amplifiers. In this CMOS image sensor, the lower-noise transistor in each pixel is selected in the readout operation using a table of determining the lower-noise transistors of all the pixels. A prototype image sensor with 65×290 pixels for demonstrating the effectiveness of this technique has been implemented using 0.18µm CMOS image sensor technology with pinned photodiode option. The measured result shows that the maximum noise using the amplifier-selection technique is reduced to 9.6e- from 17.2e- which is the maximum noise of the image array using one of two amplifiers in each pixel without selection.
Study on the Structural Strength of Deep Well Rail Car in Railway Applications (2016)

Stress tests were conducted in the carbody of the railroad car to check the structural strength of the body of the railroad car. The objective of this study was to evaluate safety of the carbody of a railroad car under the maximal strength. The carbody of rolling stock is a principal structure that supports major equipment of the underframe and the freight. Therefore, the strength evaluation of this structure is important. This study was carried out to analyze the structure of carbody and evaluate safety under maximum vertical load, compressive load, and torsional load. Accordingly, stress tests were conducted on the carbody to measure the stress on each of their parts. Before the load test, a structural-analysis program was used for the stress distribution analysis of the body structure.
Preparation and Properties of Oligomeric Siloxane-Grafted Silica Nanoparticles in a Dry Surface Treatment System (2016)

For the purpose of the prevention of environmental pollution and the simplification of reaction process, the dry surface treatment system and carefully controlled synthesis of oligomeric siloxane (oligo-SiO) was investigated. The grafting of the oligo-SiOs onto the silica surface was successfully achieved. The oligo-SiOs made by both bifunctional silane and tetrafunctional silane contained many hydroxyl groups that led to the higher chemical grafting efficiency. By grafting of oligo-SiO containing moderate number of phenyl groups onto the surface, the silica was easily dispersed in mixed solvent of toluene/ethyl acetate. In addition, the oligo-SiO-grafted silica dispersed in a composite polyimide film had excellent adhesion ability to a silicon chip.
Guidance of pharmacotherapy in a complex psychiatric case by CYP450 DNA typing (2011)

In complex cases, CYP450 DNA testing can guide pharmacotherapy by exposing innate hepatic metabolic deficiencies as a result of DNA polymorphism. In such cases, clinicians can favor treatments that target functional isoenzyme pathways rather than deficient or null pathways thus leading to decreased risk of ADRs and improved patient response.