gebhart/patrepeval huggingface dataset:
A content-aware block placement algorithm for reducing PRAM storage bit writes (2010)

Phase-change random access memory (PRAM) is a promising storage-class memory technology that has the potential to replace flash memory and DRAM in many applications. Because individual cells in a PRAM can be written independently, only data cells whose current values differ from the corresponding bits in a write request need to be updated. Furthermore, when a block write request is received, the PRAM may contain many free blocks that are available for overwriting, and these free blocks will generally have different contents. For this reason, the number of bit programming operations required to write new data to the PRAM (and consequently power consumption and write bandwidth) depends on the location that is chosen to be overwritten. This paper describes a block placement algorithm for reducing PRAM bit writes based on the idea of indexing free blocks using a content-based signature; computing the signature value of a new block of data to be written allows a free block with similar contents to be located quickly. While the benefit that can be realized by the use of any block placement algorithm is heavily dependent on the workload, our evaluation results show that block placement using content-based signatures is able to reduce the number of PRAM bit programming operations by as much as an order of magnitude.
Non‐Redundant Roles of T Cell Costimulation Pathways in Inflammatory Arthritis Revealed by Dual Blockade of ICOS and CD28 with Acazicolcept (ALPN‐101) (2023)

Both CD28 and ICOS signaling play critical roles in inflammatory arthritis. Therapeutic agents such as acazicolcept that coinhibit both ICOS and CD28 signaling may mitigate inflammation and/or disease progression in RA and PsA more effectively than inhibitors of either pathway alone.
Epitope Mapping of the Hemagglutinin Molecule of a Highly Pathogenic H5N1 Influenza Virus by Using Monoclonal Antibodies (2007)

We mapped the hemagglutinin (HA) antigenic epitopes of a highly pathogenic H5N1 influenza virus on the three-dimensional HA structure by characterizing escape mutants of a recombinant virus containing A/Vietnam/1203/04 (H5N1) deltaHA and neuraminidase genes in the genetic background of A/Puerto Rico/8/34 (H1N1) virus. The mutants were selected with a panel of eight anti-HA monoclonal antibodies (MAbs), seven to A/Vietnam/1203/04 (H5N1) virus and one to A/Chicken/Pennsylvania/8125/83 (H5N2) virus, and the mutants' HA genes were sequenced. The amino acid changes suggested three MAb groups: four MAbs reacted with the complex epitope comprising parts of the antigenic site B of H3 HA and site Sa of H1 HA, two MAbs reacted with the epitope corresponding to the antigenic site A in H3 HA, and two MAbs displayed unusual behavior: each recognized amino acid changes at two widely separate antigenic sites. Five changes were detected in amino acid residues not previously reported as changed in H5 escape mutants, and four others had substitutions not previously described. The HA antigenic structure differs substantially between A/Vietnam/1203/04 (H5N1) virus and the low-pathogenic A/Mallard/Pennsylvania/10218/84 (H5N2) virus we previously characterized (N. V. Kaverin et al., J. Gen. Virol. 83:2497-2505, 2002). The hemagglutination inhibition reactions of the MAbs with recent highly pathogenic H5N1 viruses were consistent with the antigenic-site amino acid changes but not with clades and subclades based on H5 phylogenetic analysis. These results provide information on the recognition sites of the MAbs widely used to study H5N1 viruses and demonstrate the involvement of the HA antigenic sites in the evolution of highly pathogenic H5N1 viruses, findings that can be critical for characterizing pathogenesis and vaccine design.
Isolation of Antibodies to Heparan Sulfate on Glypicans by Phage Display (2018)

Heparan sulfate (HS) plays an important role in development and disease. It interacts with many growth factors, chemokines, and other ligands known to be important for cell growth, motility, and differentiation. However, isolating an antibody to HS in mice, rabbits, or humans is difficult due to the poor immunogenicity of HS. Phage display is a major antibody engineering technology that allows the selection of antibodies for poorly immunogenic or highly conserved antigens. This protocol contains detailed procedures for HS antigen preparation and isolation of a phage displayed human single-chain Fv (HS20) that binds HS on glypican-3 (GPC3), and analysis of the selected phage antibody. It is conceivable that the procedures described in this protocol may be applicable to the isolation of antibodies for a variety of HS molecules. © 2018 by John Wiley & Sons, Inc.
NeuroXplorer 1.0: An Extensible Framework for Architectural Exploration with Spiking Neural Networks (2021)

Recently, both industry and academia have proposed many different neuromorphic architectures to execute applications that are designed with Spiking Neural Network (SNN). Consequently, there is a growing need for an extensible simulation framework that can perform architectural explorations with SNNs, including both platform-based design of today’s hardware, and hardware-software co-design and design-technology co-optimization of the future. We present NeuroXplorer, a fast and extensible framework that is based on a generalized template for modeling a neuromorphic architecture that can be infused with the specific details of a given hardware and/or technology. NeuroXplorer can perform both low-level cycle-accurate architectural simulations and high-level analysis with data-flow abstractions. NeuroXplorer’s optimization engine can incorporate hardware-oriented metrics such as energy, throughput, and latency, as well as SNN-oriented metrics such as inter-spike interval distortion and spike disorder, which directly impact SNN performance. We demonstrate the architectural exploration capabilities of NeuroXplorer through case studies with many state-of-the-art machine learning models.
Supplementary Figure 4 from An Oncogenic Role for <i>ETV1</i> in Melanoma (2023)

Supplementary Figure 4 from An Oncogenic Role for &lt;i&gt;ETV1&lt;/i&gt; in Melanoma
Microbial Transformation of (+)-10β,14-Dihydroxy-allo-aromadendrane and (−)-allo-Aromadendrone (1999)

The biotransformation of (+)-10β,14-dihydroxy-allo-aromadendrane 1 and (–)-allo-aromadendrone 2 by Beauvaria densa CMC 3240, Beauvaria bassiana ATCC 7159, Curvularia lunata 2380 and Rhizopus sp. (from grapes) is investigated.
Reaction rates for the chemiluminescence of Cypridina luciferin analogues with superoxide: A quenching experiment with superoxide dismutase. (1991)

Reaction rate constants for Superoxide (O2-) with Cypridina luciferin analogues (CLAs), 2-methyl-6-phenyl- and 2-methyl-6-(p-methoxyphenyl)-3, 7-dihydroimidazo[1, 2-a]pyrazin-3-ones (CLA and MCLA), and 2-methyl-6-[p-[2-[sodium 3-carboxylato-4-(6-hydroxy-3-xanthenon-9-yl)-phenylthioureylene]ethyleneoxy]phenyl]-3, 7-dihydroimidazo[1, 2-a]pyrazin-3-one(FCLA), were determined for the first time by using superoxide dismutase (SOD) for a quencher as 1.08 × 108, 2.54 × 108 and 8.5 × 107 M-1 sec-1 in pH 7.1 buffer solutions at 25°C.
Zuclopenthixol Treatment of Behavioral Disturbances in Mentally Retarded Children and Adolescents: An Open-Label Study (2001)

The present open-label study assessed the efficacy of zuclopenthixol, an thioxanthene neuroleptic with combined dopamine receptors (D1/D2) antagonist activity, in the treatment of severe behavioral disturbances in mentally retarded children and adolescents. A sample of 15 (11 males, 4 females) mentally retarded children and adolescents, ages 5-18 years (12.2 +/- 2.3 [mean +/- SD] years), all exhibiting severe behavioral disturbances, was evaluated. The 12-week zuclopenthixol treatment (up to 26 mg/day) was initiated after a week's washout from previous antipsychotic agents. An assessment of the behavioral disturbances was performed using the 14-item Checklist for Behavior Problems Involving Limited or No Social Awareness (CBP-NSA). The Udvalg for kliniske undersøgelser (UKU) Side Effect Rating Scale was used to assess the pharmacologic side effects. Results show a significant reduction in total CBP-NSA scores and in individual items such as hyperactivity, aggressive behavior, and temper tantrums (p < 0.001 for each). It seems that zuclopenthixol monotherapy is effective and well tolerated in the treatment of severe behavioral disturbances in mentally retarded children and adolescents. Double-blind, placebo-controlled studies are needed before definitive conclusions can be drawn regarding the efficacy and safety of zuclopenthixol for this population.
Novel pharmacodynamic biomarkers for MYCN protein and PI3K/AKT/mTOR pathway signaling in children with neuroblastoma (2015)

There is an urgent need for improved therapies for children with high-risk neuroblastoma where survival rates remain low. MYCN amplification is the most common genomic change associated with aggressive neuroblastoma and drugs targeting PI3K/AKT/mTOR, to activate MYCN oncoprotein degradation, are entering clinical evaluation. Our aim was to develop and validate pharmacodynamic (PD) biomarkers to evaluate both proof of mechanism and proof of concept for drugs that block PI3K/AKT/mTOR pathway activity in children with neuroblastoma. We have addressed the issue of limited access to tumor biopsies for quantitative detection of protein biomarkers by optimizing a three-color fluorescence activated cell sorting (FACS) method to purify CD45-/GD2+/CD56+ neuroblastoma cells from bone marrow. We then developed a novel quantitative measurement of MYCN protein in these isolated neuroblastoma cells, providing the potential to demonstrate proof of concept for drugs that inhibit PI3K/AKT/mTOR signaling in this disease. In addition we have established quantitative detection of three biomarkers for AKT pathway activity (phosphorylated and total AKT, GSK3β and P70S6K) in surrogate platelet-rich plasma (PRP) from pediatric patients. Together our new approach to neuroblastoma cell isolation for protein detection and suite of PD assays provides for the first time the opportunity for robust, quantitative measurement of protein-based PD biomarkers in this pediatric patient population. These will be ideal tools to support clinical evaluation of PI3K/AKT/mTOR pathway drugs and their ability to target MYCN oncoprotein in upcoming clinical trials in neuroblastoma.
Prediction of high-performance on-chip global interconnection (2009)

Different interconnection structures have been proposed to solve the performance limitation caused by scaling of on-chip global wires. In this paper, we give an overview of current on-chip global interconnection structures and provide a simple model to analyze their architecture-level performance metrics. For a new category of global interconnections using on-chip transmission-line (T-line), a general framework is proposed to design and optimize such schemes. A group of experiments is performed to study and compare five different global interconnection structures in terms of latency, energy dissipation, throughput, and signal integrity across multiple technology nodes. The results show that, the T-line structures have the potential to outperform repeated RC wires at future nodes to achieve high-performance, low-power and more reliable global interconnection. Meanwhile, equalization could be helpful to improve the throughput, signal integrity, and power efficiency further.
Data from <i>MDM2</i> Derived from Dedifferentiated Liposarcoma Extracellular Vesicles Induces MMP2 Production from Preadipocytes (2023)

&lt;div&gt;Abstract&lt;p&gt;Dedifferentiated liposarcoma (DDLPS) is frequently diagnosed late, and patients typically respond poorly to treatments. DDLPS is molecularly characterized by wild-type p53 and amplification of the &lt;i&gt;MDM2&lt;/i&gt; gene, which results in overexpression of MDM2 protein, a key oncogenic process in DDLPS. In this study, we demonstrate that extracellular vesicles derived from patients with DDLPS or from DDLPS cell lines are carriers of MDM2 DNA that can be transferred to preadipocytes, a major and ubiquitous cellular component of the DDLPS tumor microenvironment, leading to impaired p53 activity in preadipocytes and increased proliferation, migration, and production of matrix metalloproteinase 2; treatment with MDM2 inhibitors repressed these effects. Overall, these findings indicate that MDM2 plays a crucial role in DDLPS by enabling cross-talk between tumor cells and the surrounding microenvironment and that targeting vesicular MDM2 could represent a therapeutic option for treating DDLPS.&lt;/p&gt;Significance:&lt;p&gt;Extracellular vesicles derived from dedifferentiated liposarcoma cells induce oncogenic properties in preadipocytes.&lt;/p&gt;&lt;/div&gt;
Built-in Potential Mapping of Silicon Field Effect Transistor Cross Sections by Multimode Scanning Probe Microscopy (2013)

Built-in potential maps of metal-oxide-semiconductor field effect transistors (MOSFETs) with gate lengths of 30 and 150 nm were measured on cross sectional Si(110) surfaces covered with ultra-thin oxide. The maps were obtained by measuring the contact potential difference (CPD) using multimode scanning probe microscopy (MSPM) with a vibrating probe in the constant force mode. The improved spatial resolution and the sensitivity to the electrostatic potential were achieved for an optimal probe-sample gap (～1 nm) and vibration amplitude of 0.2 nm. The capability and challenges of the measurement method are discussed by comparing measured CPD maps with device simulation results.
Use of a rapid digital microfluidics-powered immunoassay for assessing measles and rubella infection and immunity in outbreak settings in the Democratic Republic of the Congo (2022)

The Democratic Republic of the Congo (DRC) has a high measles incidence despite elimination efforts and has yet to introduce rubella vaccine. We evaluated the performance of a prototype rapid digital microfluidics powered (DMF) enzyme-linked immunoassay (ELISA) assessing measles and rubella infection, by testing for immunoglobulin M (IgM), and immunity from natural infection or vaccine, by testing immunoglobulin G (IgG), in outbreak settings. Field evaluations were conducted during September 2017, in Kinshasa province, DRC. Blood specimens were collected during an outbreak investigation of suspected measles cases and tested for measles and rubella IgM and IgG using the DMF-ELISA in the field. Simultaneously, a household serosurvey for measles and rubella IgG was conducted in a recently confirmed measles outbreak area. DMF-ELISA results were compared with reference ELISA results tested at DRC's National Public Health Laboratory and the US Centers for Disease Control and Prevention. Of 157 suspected measles cases, rubella IgM was detected in 54% while measles IgM was detected in 13%. Measles IgG-positive cases were higher among vaccinated persons (87%) than unvaccinated persons (72%). In the recent measles outbreak area, measles IgG seroprevalence was 93% overall, while rubella seroprevalence was lower for children (77%) than women (98%). Compared with reference ELISA, DMF-ELISA sensitivity and specificity were 82% and 78% for measles IgG; 88% and 89% for measles IgM; 85% and 85% for rubella IgG; and 81% and 83% for rubella IgM, respectively. Rubella infection was detected in more than half of persons meeting the suspected measles case definition during a presumed measles outbreak, suggesting substantial unrecognized rubella incidence, and highlighting the need for rubella vaccine introduction into the national schedule. The performance of the DMF-ELISA suggested that this technology can be used to develop rapid diagnostic tests for measles and rubella.
Supp Fig 3 from Pexmetinib: A Novel Dual Inhibitor of Tie2 and p38 MAPK with Efficacy in Preclinical Models of Myelodysplastic Syndromes and Acute Myeloid Leukemia (2023)

&lt;p&gt;Proposed model of efficacy of dual inhibitor of Tie2 and p38 MAPK in MDS and AML&lt;/p&gt;
Proteinases of Legionella: Phenylalanineaminopeptidase of L. pneumophila (1986)

Phenylalanineaminopeptidase was isolated and purified from the culture filtrate of Legionella pneumophila by affinity chromatography on O-tert-butyl-L-threonyl-L-phenylalanyl-L-prolylglycyl-aminosilo chrom and by gel-filtration; a 401-fold purification with a yield of 18% was achieved. The enzyme was a metalloenzyme with a molecular weight of 35000 and a pI of 5.8. It was stable at pH 7-9 and had an activity optimum in the range of pH 8-9.5 with L-phenylalanine p-nitroanilide as substrate. Enzyme activity was highest towards the latter compound, substantially lower towards L-leucine p-nitroanilide and only marginal towards other p-nitroanilides. Besides phenylalanineaminopeptidase, a metalloproteinase and a serine proteinase were also detected in L. pneumophila culture filtrate.
Predictors of 18F-DCFPyL PET/CT Positivity in Patients with Biochemical Recurrence of Prostate Cancer After Local Therapy (2021)

Our objective was to investigate the factors predicting scan positivity and disease location in patients with biochemical recurrence (BCR) of prostate cancer (PCa) after primary local therapy using prostate-specific membrane antigen-targeted <sup>18</sup>F-DCFPyL PET/CT. <b>Methods:</b> This was a 2-institution study including 245 BCR PCa patients after primary local therapy and negative results on conventional imaging. The patients underwent <sup>18</sup>F-DCFPyL PET/CT. We tested for correlations of lesion detection rate and disease location with tumor characteristics, time from initial therapy, prostate-specific antigen (PSA) level, and PSA doubling time (PSAdt). Multivariate logistic regression analyses were used to determine predictors of a positive scan. Regression-based coefficients were used to develop nomograms predicting scan positivity and extrapelvic disease. <b>Results:</b> Overall, 79.2% (194/245) of patients had a positive <sup>18</sup>F-DCFPyL PET/CT result, with detection rates of 48.2% (27/56), 74.3% (26/35), 84% (37/44), 96.7% (59/61), and 91.8% (45/49) for PSAs of <0.5, 0.5 to <1.0, 1.0 to <2.0, 2.0 to <5.0, and ≥5.0 ng/mL, respectively. Patients with lesions confined to the pelvis had lower PSAs than those with distant sites (1.6 ± 3.5 vs. 3.0 ± 6.3 ng/mL, <i>P</i> < 0.001). In patients treated with prostatectomy (<i>n</i> = 195), 24.1% (47/195) had a negative scan result, 46.1% (90/195) showed intrapelvic disease, and 29.7% (58/195) showed extrapelvic disease. In the postradiation subgroup (<i>n</i> = 50), <sup>18</sup>F-DCFPyL PET/CT was always negative at a PSA lower than 1.0 ng/mL and extrapelvic disease was seen only when PSA was greater than 2.0 ng/mL. At multivariate analysis, PSA and PSAdt were independent predictive factors of scan positivity and the presence of extrapelvic disease in postsurgical patients, with area under the curve of 78% and 76%, respectively. PSA and PSAdt were independent predictors of the presence of extrapelvic disease in the postradiation cohort, with area under the curve of 85%. Time from treatment to scan was significantly longer for prostatectomy-bed-only recurrences than for those with bone or visceral disease (6.2 ± 6.4 vs. 2.4 ± 1.3 y, <i>P</i> < 0.001). <b>Conclusion:</b><sup>18</sup>F-DCFPyL PET/CT offers high detection rates in BCR PCa patients. PSA and PSAdt are able to predict scan positivity and disease location. Furthermore, the presence of bone or visceral lesions is associated with shorter intervals from treatment than are prostate-bed-only recurrences. These tools might guide clinicians to select the most suitable candidates for <sup>18</sup>F-DCFPyL PET/CT imaging.
EMD 1214063 and EMD 1204831 Constitute a New Class of Potent and Highly Selective c-Met Inhibitors (2013)

Our results indicate selective c-Met inhibition by EMD 1214063 and EMD 1204831 and strongly support clinical testing of these compounds in the context of molecularly targeted anticancer strategies.
Phase I study of pembrolizumab in people with HIV and cancer. (2019)

2500 Background: People with HIV have been excluded from immuno-oncology (IO) studies. Anti- PD-1/PD-L1 therapies are approved for a growing number of cancers. We evaluated pembrolizumab (pembro) in people with HIV and cancer. Methods: CITN-12 is a multicenter phase 1 trial. Key eligibility: advanced cancer; ECOG ≤1; CD4 ≥100 cells/μL; ≥4 weeks antiretroviral therapy (ART), HIV viral load (VL) &lt; 200 copies/mL. Exclusion: uncontrolled HBV/HCV, autoimmune disease. Participants (pts) accrued into CD4 based cohorts (C): C1 100-199; C2 200-350; C3 &gt; 350 CD4 cells/μL. Pembro 200 mg IV administered Q3W for up to 35 doses. Adverse events (AE) evaluated by CTCAE. Immune related AE ≥ grade (Gr) 2 were events of clinical interest (irECI). Clinical benefit (tumor shrinkage or stable disease [SD] ≥24 weeks) was estimated. Data were locked for safety analysis and publication once C2 and C3 completed accrual and all pts completed ≥2 cycles. Accrual continued for 6 C1 pts and a new phase 1b Kaposi sarcoma (KS) cohort (C4). Results: 30 pts, characteristics: C1 (6), C2 and 3 (12 each), median (med) age 57 years (range 39-77), 28 men, 2 women, 60% White, 30% Black, 10% Hispanic. Med CD4 285 cells/μL (132 - 966). Cancers: KS (6), non-Hodgkin lymphoma (NHL) (5), non-AIDS defining (19) – most common: anal (6) and squamous cell skin (3). Prior radiation (19), med prior systemic therapies 2 (0-8). Safety observed over 183 cycles, med 5 (1-32). Treatment emergent AE ≥ possibly attributed to pembro mostly Gr 1-2, with 20% of pts having Gr 3. irECI: hypothyroidism (6), elevated AST/ALT (1), pneumonitis (3), rash (2), musculoskeletal (1).1 KS pt developed KSHV-associated multicentric Castleman disease (KSHV-MCD) and died of the AE. HIV was controlled and increasing CD4 counts were observed. Best response: complete (lung, 1), partial (NHL, 2), SD ≥24 weeks (KS, 2), SD &lt; 24 weeks (13), progressive disease (10), not evaluable (2). Conclusions: Pembro has acceptable safety in cancer pts with HIV on ART and &gt; 100 CD4 cells/µL, similar to patients without HIV. Anti-PD-1 may unmask KSHV-MCD and such KSHV-viremic patients should be excluded. Clinical benefit was noted in several tumor types. Anti-PD1 is appropriate for FDA-approved indications in this population. Patients with HIV meeting appropriate eligibility criteria should be included in IO studies. Clinical trial information: NCT02595866.
15. EPRI Contribution to International Utility Industry Seismic Isolation Development Program (1990)

Seismic isolation was selected as a potential method of increasing the structural integrity margins for liquid metal reactor power plants. Analyses indicated that seismic isolation would reduce by 90 to 95% the acceleration experienced by the reactor vessel at its fundamental frequency. A cooperative development program was established by electric utility organizations in Japan, the United Kingdom and the United States. Alternative seismic isolator concepts were compared and the laminated elastomer/steel with lead plug concept was selected to be the first concept tested. Sixteen half‐sized units were tested, the results compared with predictions and potential isolator design improvements inferred. The cooperative program is continuing through testing of other isolator concepts.