gebhart/patrepeval huggingface dataset:
Design, Synthesis, and Biological Evaluation of NAP Isosteres: A Switch from Peripheral to Central Nervous System Acting Mu-Opioid Receptor Antagonists (2022)

The μ opioid receptor (MOR) has been an intrinsic target to develop treatment of opioid use disorders (OUD). Herein, we report our efforts on developing centrally acting MOR antagonists by structural modifications of 17-cyclopropylmethyl-3,14-dihydroxy-4,5α-epoxy-6β-[(4'-pyridyl) carboxamido] morphinan (NAP), a peripherally acting MOR-selective antagonist. An isosteric replacement concept was applied and incorporated with physiochemical property predictions in the molecular design. Three analogs, namely, <b>25</b>, <b>26</b>, and <b>31</b>, were identified as potent MOR antagonists <i>in vivo</i> with significantly fewer withdrawal symptoms than naloxone observed at similar doses. Furthermore, brain and plasma drug distribution studies supported the outcomes of our design strategy on these compounds. Taken together, our isosteric replacement of pyridine with pyrrole, furan, and thiophene provided insights into the structure-activity relationships of NAP and aided the understanding of physicochemical requirements of potential CNS acting opioids. These efforts resulted in potent, centrally efficacious MOR antagonists that may be pursued as leads to treat OUD.
Is the Pen Mightier than the Controller? A Comparison of Input Devices for Selection in Virtual and Augmented Reality (2019)

Controllers are currently the typical input device for commercial Virtual Reality (VR) systems. Yet, such controllers are not as efficient as other devices, including the mouse. This motivates us to investigate devices that substantially exceed the controller’s performance, for both VR and Augmented Reality (AR) systems. We performed a user study to compare several input devices, including a mouse, controller, and a 3D pen-like device on a VR and AR pointing task. Our results show that the 3D pen significantly outperforms modern VR controllers in all evaluated measures and that it is comparable to the mouse. Participants also liked the 3D pen more than the controller. Finally, we show how 3D pen devices could be integrated into today’s VR and AR systems.
Linear prediction based comfort noise generation in the EVS codec (2015)

A Discontinuous transmission (DTX) system, which is widely adopted in speech codecs, is an important function for speech communication systems that can reduce the transmission bandwidth by at least a half. Within a DTX system, the comfort noise generation (CNG) plays a key role in the overall quality. Critical performance parameters with respect to the CNG including the transition quality from active to comfort noise (CN) frame, the quality of CN spectrum estimation, wider bandwidth rendering and the DTX efficiency have all been found to be very important. This paper describes a series of new technologies developed for the EVS codec aiming to address the performance of the CNG: A new hangover based CN analysis technique provides improved CNG transition quality. A new entropy based CN spectrum estimation technique and a new hybrid CNG scheme improve the CN spectrum estimation. Finally, a novel bandwidth extension technique for efficient rendering of high-frequency CN and a novel technique improving the DTX efficiency by controlling the DTX hangover length are described.
Identification of an Immunodominant IgE Epitope of the Parietaria judaica Major Allergen (1998)

Par j 1.0101 is one of the two major allergens of the Parietaria judaica (Pj) pollen, and its three-dimensional structure was built by three-dimensional structural homology modeling. The resultant model was used to identify putative IgE binding regions. Western blot analysis of gene fragmentation products showed that the 1 to 30 region was capable of binding specific IgE from a pool of sera (n = 30) of patients allergic to Pj pollen. Using the structural model as a guide, deletion and site-directed mutagenesis of the 1 to 30 region was performed, and the amino acids involved in IgE binding were identified. In addition, a synthetic peptide covering the 1 to 30 region was capable of binding human IgE without triggering histamine release from basophils of Pj allergic patients (n = 6) and thus represents a haptenic molecule with potential use as an immunotolerant agent. This epitope is also present on the Par j 2.0101 major allergen representing a common IgE epitope. It is an immunodominant epitope, since it was capable of inhibiting 30% of all specific IgE against the Pj major allergens, and therefore, it might be a candidate for the future development of immunotherapeutics.
A phase II evaluation of temsirolimus in combination with carboplatin and paclitaxel followed by temsirolimus consolidation as first-line therapy in the treatment of stage III-IV clear cell carcinoma of the ovary. (2016)

5531 Background: The primary objective of the study is to estimate the 12-month progression-free survival (PFS) for carboplatin/paclitaxel + temsirolimus in women with newly diagnosed clear cell ovarian cancer (CCOC) and to compare to historical controls in this patient population from previous GOG protocols. Methods: Patients with Stage III or IV CCOC were enrolled. Patients were treated with Paclitaxel 175 mg/m2 on Day 1, Carboplatin AUC 6 Day 1, and Temsirolimus (CCI-779) 25mg IV Days 1 and 8 every 3 weeks for Cycles 1-6 or disease progression, followed by consolidation therapy with temsirolimus 25 mg Days 1, 8, and 15 every 3 weeks cycles 7-17 or until disease progression. All eligible patients who received therapy were evaluated for efficacy and toxicity. Results: Ninety patients were accrued to the study: 45 in the US and Korea (US/Korea) and 45 in Japan. Efficacy is presented separately for US/Korea and Japan. Most (83%) patients were stage III, and 66% of patients had no measurable disease starting therapy. Twenty-two percent received < 6 cycles of therapy while 28% completed all 17 cycles of chemotherapy. In patients with measurable disease, in the US/Korea, 31% (n = 4) and 23% (n = 3) had complete or partial responses, respectively, while in Japan, 6% (n = 1) and 65% (n = 11) did. Median PFS (OS) was 11 (23) months for US/Korea and 12 (26) months for Japan. Most (85%) patients (88% US/Korea, 82% Japan) were optimally debulked. In the US, 0% of suboptimally debulked patients had PFS > 12 months, and 49% of optimal patients did; in Japan, these were 25% and 59%. In neither the US/Korea nor Japan was the 12-month PFS significantly (p > 0.05) better than historical controls. There was no statistically significant difference in PFS or OS between US/Korea and Japan. Most common G3-4 adverse events were neutropenia, leukopenia, anemia, and thrombocytopenia. Conclusions: Carboplatin/paclitaxel + temsirolimus was well tolerated. Optimally debulked patients benefited most, with 54% having a PFS > 12 months. When compared to historical controls this regimen did not statistically significantly increase PFS at 12 months. Clinical trial information: NCT01196429.
Comparison of different means of providing oxygen to a biobarrier to be used for the degradation of MTBE. (2004)

NRC publication: Yes
TLM analysis of a dielectric loaded antenna with a balanced feed (2002)

In this paper the transmission line matrix (TLM) technique is used to assess the dielectric loaded bifilar antenna. This antenna is suitable for personal mobile communications and is analysed using a commercial electromagnetic software package.
TP53 mutations emerge in circulating cell-free DNA obtained from patients undergoing treatment with the HDM2 antagonist SAR405838. (2015)

2515 Background: SAR405838 is an oral antagonist of HDM2 that results in p53 induction. In an ongoing Phase I study, p53 activation was demonstrated at doses that have an acceptable safety profile. We sought to develop a method for sequencing circulating cell-free DNA (ccfDNA) for the non-invasive monitoring of genetic changes in the tumor that may impact the activity of SAR405838 Methods: Baseline tumor and serially collected plasma samples were obtained from de-differentiated liposarcoma (DDLPS) patients undergoing treatment with SAR405838 at the maximum tolerated dose (300 mg QD). Tumor biopsies were sequenced using the Ion AmpliSeq Cancer Hotspot Panel v2 (Life Technologies). A custom next-generation sequencing targeted gene panel was developed for ccfDNA. Sequencing libraries were prepared using custom xGen Lockdown probes (IDT). Sequencing was performed using the Illumina HiSeq 2500. Mutations were determined using a custom pipeline combining calls from MuTec and Lofreq. Mutation confirmation was performed using RainDance droplet digital PCR. Results: Tumor and plasma samples were available from 18 patients. All tumors were determined to be TP53 wild-type at baseline. From ccfDNA, greater than 10,000X coverage of target sequence was achieved. No TP53 mutations were identified at variant allele frequency (VAF) > 1% in the baseline ccfDNA samples. 27 non-synonymous mutations in TP53 were identified at VAF > 1% in ccfDNA from patients undergoing treatment. All TP53 mutations were previously reported in COSMIC, and all are located in the DNA-binding domain of p53. Mutation VAF increased during treatment, and multiple TP53 mutations arose within individual patients. All patients undergoing 5 or more cycles of treatment showed evidence of TP53 mutations in ccfDNA. A subset of mutations was selected for validation and all were confirmed using digital PCR. Conclusions: TP53 mutations appear in the ccfDNA of patients during treatment with SAR405838. This may represent the selection of TP53 mutant clones that are resistant to HDM2 inhibition. This finding suggests that HDM2 antagonists should be combined with other mechanisms including agents active in p53 mutant tumors.
Supplementary Figure 3 from Loss of PPP2R2A Inhibits Homologous Recombination DNA Repair and Predicts Tumor Sensitivity to PARP Inhibition (2023)

&lt;p&gt;PDF file - 33K, Suppression of PP2A regulatory subunits by specific shRNAs&lt;/p&gt;
Characterisation of Stability Criteria for Pressure Driven Flows in Small Length Scale Fluidic Devices (2005)

This paper develops criteria for the prediction of two distinct instabilities in microflows, one isothermal, the other with heat transfer. The engineering objective is to transport droplets that act as micro-reactors and are carried through various processes in a carrier fluid to prepare sample reactants or complete a chemical reaction. The requirement is that the carrier fluid flow be stable so that droplet trajectories can be accurately controlled. The popular two-dimensional microfluidic geometry of three streamlines merging at a junction is chosen for this analysis. A dimensional analysis of the governing flow-field and boundary conditions is undertaken to derive the non-dimensional groups upon which the flow characteristics of the junction are dependent. The emerging parameters are the Grasshof number (Gr) and Reynolds numbers (Re) of both inlet streams. Experimental flow visualisation images are used to determine the relationship between these scaling groups for both isothermal flow and buoyancy opposing mixed convection. The experimental range of inlet Re’s is from 1 to 100. It is found that the ratio of the inlet Re’s is sufficient to describe isothermal flows and that a parameter referred to as W* (the product of the Richardson number (Ri) and Re of the centreline stream) provides a good correlation for buoyancy opposing mixed convection. Inertia dominated flow regimes are seen to exist for W* values below approximately 2 and re-circulation zones are observed when W* is increased above this value. It was also observed that buckling flow was attainable at a critical Re of 65 for isothermal flow and that this critical Re is significantly reduced as W* is increased. An analogy is drawn from the results between the flow studied in this paper and that of cross flow over bluff objects such as a cylinder. Finally, based on the results of this work a design envelope is developed for predicting the stability of scaled models of the fluidic junction.
A Pragmatic Approach for Reducing Delays in Publishing Documents within the Real-time Applications and Infrastructure (RAI) Area (2009)

During the last year, participants in the Real-time Applications and
Infrastructure (RAI) area have been quite active in discussing
proposals that could improve their way of working. This document is a
contribution to that discussion and focuses on the reduction of delays
experienced in producing specifications. We believe that this is one
of the main problems in the RAI area (and quite likely in other areas
of the IETF as well) and it requires attention. A number of side
effects, caused by the long specification work, are illustrated in
this document.
Dunkelfeld-Computertomographie – Erster Proof of Principle in einem Human CT (2023)

Zielsetzung Die Dunkelfeldbildgebung mit Röntgenstrahlen ist ein neuartiges interferometrisches Verfahren, das eine Visualisierung der Alveolarstruktur ermöglicht. Im klinischen Kontext ist das Verfahren bislang auf radiographische Anwendungen beschränkt und konnte noch nicht für CT Bildgebung umgesetzt werden. In ersten Studien konnte bereits gezeigt werden, dass die Dunkelfeld-Bildgebung des Thorax konventionelle Radiographie ergänzt und verbessert. Ziel dieser technischen Machbarkeitsstudie ist es daher, einen Dunkelfeld-CT-Prototyp für Thorax Scans zu entwickeln. Für einen potentiellen klinischen Einsatz muss ein solcher Scanner dosiskompatible und schnelle Messungen im Sekundenbereich ermöglichen.
Abstract 3111: The ETS factor ETV1 is an oncogene in melanoma (2010)

Abstract Chromosome 7 copy gains are a recurrent genomic alteration in melanoma. Previous genomic studies identified a common peak of gain within 7p, highlighting it as a region likely to contain “driver” cancer genes. In this study, we identified several melanoma samples with focal amplification events located within this peak, and found that the overlapping region of these amplicons contained the locus of the ETS transcription factor and oncogene, ETV1. Fluorescent in situ hybridization analysis of a progressive melanoma tissue microarray revealed ETV1 amplification in 13% of the primary tumors and 18%of the metastatic melanomas, whereas no amplification in nevus samples. Silencing of ETV1 expression demonstrated dependency on ETV1 expression for proliferation and anchorage-independent growth in some melanoma cell lines. Moreover, over-expression of ETV1 in combination with oncogenic NRASG12D transformed primary melanocytes and promoted tumor formation in mice. Interestingly, overexpression of ETV1 increased MITF expression, a known oncogene in melanoma. Together, these observations suggest an oncogenic role for ETS transcription factors in general and ETV1 in particular in melanoma. 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 3111.
Spontaneous Calcification in F34/Slc and F344/JCL Rats (1986)

F344/Slc and F344/JCL rats 2 years of age were histologically examined for the incidence and distribution of calcification. In the male rats of both strains, calcification was observed in the testis, lung, brain, kidney, heart, aorta, cornea, prostate and seminal vesicle respectively. In the female F344/JCL rats, calcification appeared in the kidney, lung, cornea, brain, stomach, ovary and heart. Among these of both sexes, the lung was one of the most affected organs for calcification. On the other hand, calcification in the kidney was more severe and frequent in the females than in the males, suggesting that the sex may be one of enhancing factors for calcification.
Capacity evaluation of transmit beamforming CDMA system with FER prediction method (2004)

The maximum SINR transmission (MST) algorithm for the forward link beamforming jointly with power control and RAKE combining have shown reduction of the total transmit power compared to maximum ratio transmission (MRT) scheme (Y.K. Choi, et al., 2002). In this paper, the user capacity and the outage performance of the transmit beamforming system according to the various number of antennas on various fading channels are evaluated for both MST and MRT schemes. In order to evaluate capacity, link level and system level simulation are jointly conducted by using FER prediction table that has been obtained from various fading channels. The FER prediction approach enables us to define the outage probability as P(FER>target FER) and study the effects of velocity of mobiles, spatial correlation of the fading channel, and the outer loop power control. The results show that the MST beamforming scheme can considerably increase the user capacity compared to the MRT scheme.
Abstract 4392: Vaccination targeting IGF-IR sensitizes tumors to tamoxifen therapy in an anti-estrogen resistant mouse model (2012)

Abstract Tamoxifen is a standard treatment for estrogen receptor (ER)-positive breast cancer patients. However, acquired or de novo resistance to therapy is a major clinical problem. In hormone-resistant tumors, there is increased activation of insulin-like growth factor-1 receptor (IGF-IR) and subsequent downstream signaling molecules, such as AKT. We have determined that IGF-IR is immunogenic in breast cancer and is a potential target for active immunization. It has been demonstrated that natural immunogenic human epitopes can be predicted by high binding affinity across multiple class II alleles, thus, we used a combined scoring system from five algorithms for predicting class II binding to determine Th epitopes of IGF-IR. Of the 20 potentially immunogenic peptides identified, five peptides (p1166-1181, p1212-1227, p1301-1316, 1307-1322 and p1311-1326) in the C-terminal domain were determined to elicit a predominantly inflammatory Th1 response compared to an immunosuppressive Th2 response in human PBMC. Overexpression of AKT induces tamoxifen resistance, while inhibition restores tamoxifen sensitivity. The tumor suppressor, PTEN, actively inhibits AKT. Data we have generated has demonstrated that vaccination restored PTEN activity in tumor cells. We questioned if modulation of PTEN could render tumors in the anti-estrogen-resistant MMTV-neu mouse model sensitive to tamoxifen therapy. Vaccination demonstrated a robust Th1 response (p&amp;lt;0.001) and concomitant inhibition of tumor growth by 85% compared to adjuvant only control animals (p&amp;lt;0.001). Treatment with tamoxifen in vaccinated tumor-bearing mice resulted in a further 38% reduction in growth (p=0.02). Thus, active immunization targeting IGF-IR may induce both immunologic and biologic effects resulting in the sensitization of the tumor to tamoxifen therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4392. doi:1538-7445.AM2012-4392
MATRIX INFRARED SPECTRA OF LiCS (1977)

Author Institution: Department of Chemistry, Rice University
Tough ion gels composed of coordinatively crosslinked polymer networks using ZIF-8 nanoparticles as multifunctional crosslinkers (2022)

Constructing crosslinked polymer networks <i>via</i> reversible interactions is a promising approach to recover the mechanical strength of damaged gels. In addition, by designing effective reversible crosslinks, the mechanical strength of the gel can be enhanced through energy dissipation based on the destruction of the crosslinks by an applied force. In this study, we introduced zeolitic imidazole framework-8 nanoparticles (ZIF-8 NPs), which acted as multifunctional crosslinkers, to provide multipoint coordination bonding with a poly(<i>N</i>,<i>N</i>-dimethylacrylamide)-based polymer network in a gel containing an ionic liquid. The mechanical strength of the gel increased with an increase in the content of ZIF-8 NPs up to 6 wt%. It was confirmed that the energy loaded onto the gel was dissipated through the desorption of the polymer network from the surface of the ZIF-8 NPs. Owing to the reversible destruction and reconstruction of the coordinative crosslinking between the polymer network and ZIF-8 NPs, the mechanical strength of the damaged gel was almost fully recovered through annealing.
Supplementary Data from Pathology-Driven Comprehensive Proteomic Profiling of the Prostate Cancer Tumor Microenvironment (2023)

&lt;p&gt;Additional method details, tables and figures to support text in the manuscript. Figure S.1 Protein yield from LCM of regions of interest. Figure S.2 Variations on data analysis in the Perseus software. Figure S.3 Incidence of Biochemical Recurrence in Sample Cohort for Immunohistochemistry. Figure S.4 Expression of significant proteins in 'normal' patient biopsy tissue. Table S1.1 Significantly changing proteins between G3 epithelia and stroma. Table S1.2 Significantly changing proteins between G4 epithelia and stroma. Table S.1.3 Significantly changing proteins between G3 and G4 epithelia Table S1.4 Significantly changing proteins between G3 and G4 Stroma&lt;/p&gt;
An empirical assessment of approaches to distributed enforcement in role-based access control (RBAC) (2011)

We consider the distributed access enforcement problem for Role-Based Access Control (RBAC) systems. Such enforcement has become important with RBAC's increasing adoption, and the proliferation of data that needs to be protected. We assess six approaches, each of which has either been proposed in the literature, or is a natural candidate for access enforcement. The approaches are: directed graph, access matrix, authorization recycling, cpol, Bloom filter and cascade Bloom filter. We consider encodings of RBAC sessions in each, and propose and justify a benchmark for the assessment. We present our results from an empirical assessment of time, space and administrative efficiency based on the benchmark. We conclude with inferences we can make regarding the best approach to access enforcement for particular RBAC deployments based on our assessment.
VCSEL-Based CMOS Integrated Optical Telemetry Link for Miniaturized Implants (2018)

Implantable wireless sensing platforms are believed to revolutionize personal health care. Such systems need to communicate implant data to a reader outside the body. Wireless communication schemes eliminate the need for wires through biological interfaces for such communication. Optical communication links can be useful for such applications due to extremely small size scale. In this letter, a telemetry scheme is presented that uses a micro-laser integrated with a complementary metal oxide semiconductor-based implantable platform. It is shown that this scheme can communicate a signal reliably from sub-mm implants to external detectors through actual tissue sample. A comparative analysis of this work with other techniques is also presented.
Selective FPR2 Agonism Promotes a Proresolution Macrophage Phenotype and Improves Cardiac Structure-Function Post Myocardial Infarction (2021)

Dysregulated inflammation following myocardial infarction (MI) leads to maladaptive healing and remodeling. The study characterized and evaluated a selective formyl peptide receptor 2 (FPR2) agonist BMS-986235 in cellular assays and in rodents undergoing MI. BMS-986235 activated G proteins and promoted β-arrestin recruitment, enhanced phagocytosis and neutrophil apoptosis, regulated chemotaxis, and stimulated interleukin-10 and monocyte chemoattractant protein-1 gene expression. Treatment with BMS-986235 improved mouse survival, reduced left ventricular area, reduced scar area, and preserved wall thickness. Treatment increased macrophage arginase-1 messenger RNA and CD206 receptor levels indicating a proresolution phenotype. In rats following MI, BMS-986235 preserved viable myocardium, attenuated left ventricular remodeling, and increased ejection fraction relative to control animals. Therefore, FPR2 agonism improves post-MI healing, limits remodeling and preserves function, and may offer an innovative therapeutic option to improve outcomes.