gebhart/patrepeval huggingface dataset:
Correlation of tumor mutational burden (TMB) with CDKN2A and TP53 mutation in HPV-negative head and neck squamous cell carcinoma (HNSCC). (2020)

6552 Background: The tumor suppressors TP53 and CDKN2A are commonly mutated or lost in HNSCC, impairing G1 checkpoints. This reduces ability to repair DNA damage arising from hypoxia, replication stress, and mutagen exposure, thus increasing TMB, a potential predictive biomarker for immunotherapy benefit. TP53 mutations can be classified as loss-of-function (LOF) with or without dominant negative (DNE) activity, gain-of-function (GOF) and benign. We investigated whether specific categories of TP53 mutation were associated with increased TMB, and whether these cooperated with CDKN2A mutation to elevate TMB. Methods: We analyzed 1010 HPV- HNSCC tumor samples (246 female) profiled with a 592-gene panel by Caris Life Sciences from 2015 to 2019. Predominant subsites were oral cavity (285), oropharynx (225) and larynx (153). TMB reflected all somatic nonsynonymous missense mutations detected. We report mean TMB per megabase (MB). Pathogenicity of TP53 and CDKN2A mutations was determined according to American College of Medical Genetics (ACMG) guidelines. We also used four alternative methods of characterizing TP53 mutations based on analysis of protein structure, public databases (IARC, ClinVar, InterVar), and publications (PMID: 25108461 and others) assessing structure-function relations. Results: 60% of cases had TP53 mutations ( TP53 mu t ) designated pathogenic by ACMG guidelines. Estimates of frequency of LOF/DNE mutations ranged from 30-42.8% of cases among the alternative classification methods. Damaging CDKN2A mutations were present in 20%. Average TMB per MB varied from 8.2/8.6 (females/males) in oral cavity cancers to 26.5/27.7 (females/males) in cancer of the lip. Mean TMB was typically higher in the presence of damaging LOF/DNE TP53 mutations or CDKN2A mutations, but not TP53 GOF mutations. Based on ACMG, for tumors with TP53 and CDKN2A wild type (WT) TMB was 8.03, for those with CDKN2A mut- only 9.82, for TP53 mut- only 10.56, and TP53 mut /CDKN2A mut 17.6 (p &lt; 0.001). For disruptive TP53 mut (Poeta algorithm), mean TMB for WT/WT was 8.67, for TP53 mut 11.31, CDKN2A mut 17.9 and TP53 mut /CDKN2A mut 15.83 (p &lt; 0.001). Conclusions: Mutation of TP53 and/or CDKN2A is associated with increased mean TMB relative to WT; mean TMB was highest for tumors bearing damaging mutations in both genes. GOF TP53 mutation was not clearly associated with increased TMB. As TMB is evaluated as a predictive biomarker in the immunotherapy of HNSCC, specific TP53/CDKN2A mutational status should also be evaluated.
Influence of the Headgroupon the Interaction of Poly(ethylene oxide)-Poly(propylene oxide) BlockCopolymers with Lipid Bilayers (2020)

The lipid headgroup\nplays an important role in the association of polymers with lipid\nbilayer membranes. Herein, we report how a glycerol headgroup versus\na choline headgroup affects the interaction of poly­(ethylene oxide)-&lt;i&gt;b&lt;/i&gt;-poly­(propylene oxide) (PEO-PPO) block copolymers with\nlipid bilayer vesicles. Unilamellar vesicles composed of phosphatidylcholine\nand phosphatidylglycerol at various molar ratios were used as model\nmembranes. The interactions between the block copolymers and lipid\nbilayers were quantified by pulsed-field gradient nuclear magnetic\nresonance (PFG-NMR) based on the distinctly different mobilities of\nfree and bound polymers. All the investigated polymer species showed\nsignificantly higher binding with 1-palmitoyl-2-oleoyl-&lt;i&gt;sn&lt;/i&gt;-glycero-3-phospho-(1′-rac-glycerol) sodium salt (POPG) liposomes\nthan with 1-palmitoyl-2-oleoyl-&lt;i&gt;sn&lt;/i&gt;-glycero-3-phosphocholine\n(POPC) liposomes, indicating stronger association with the glycerol\nheadgroup compared to the choline headgroup. This effect did not become\nsignificant until the composition of mixed POPC/POPG liposomes contained\nmore than 20 mol % POPG. A plausible explanation for the enhanced\npolymer binding with POPG invokes the role of hydrogen bonding between\nthe glycerol headgroup and the ether moieties of the polymers.
PEGylated Chitosan Nanoparticles Encapsulating Ascorbic Acid and Oxaliplatin Exhibit Dramatic Apoptotic Effects against Breast Cancer Cells (2022)

This study aims to design a pH-responsive dual-loaded nanosystem based on PEGylated chitosan nanoparticles loaded with ascorbic acid (AA) and oxaliplatin (OX) for the effective treatment of breast cancer. In this regard, non-PEGylated and PEGylated chitosan nanoparticles (CS NPs) loaded with either ascorbic acid (AA), oxaliplatin (OX), or dual-loaded with AA-OX were fabricated using the ionotropic gelation method. The hydrodynamic diameters of the fabricated AA/CS NPs, OX/CS NPs, and AA-OX/CS NPs were 157.20 ± 2.40, 188.10 ± 9.70, and 261.10 ± 9.19 nm, respectively. While the hydrodynamic diameters of the designed AA/PEG-CS NPs, OX/PEG-CS NPs, and AA-OX/PEG-CS NPs were 152.20 ± 2.40, 156.60 ± 4.82, and 176.00 ± 4.21 nm, respectively. The ζ-potential of the prepared nanoparticles demonstrated high positive surface charges of +22.02 ± 1.50, +22.58 ± 1.85 and +40.4 ± 2.71 mV for AA/CS NPs, OX/CS NPs, and AA-OX/CS NPs, respectively. The ζ-potential of the PEGylated CS NPs was reduced owing to the shielding of the positive charges by the PEG chains. Additionally, all the prepared nanoparticles exhibited high entrapment efficiencies (EE%) and spherical-shaped morphology. The chemical features of the prepared nanoparticles were investigated using Fourier transform infrared (FTIR) spectroscopy. Release studies showed the capability of the prepared non-PEGylated and PEGylated chitosan NPs to release their cargo in the acidic environment of cancer tissue (pH 5.5). Furthermore, the AA/CS NPs, AA/PEG-CS NPs, OX/CS NPs, OX/PEG-CS NPs, AA-OX/CS NPs and AA-OX/PEG-CS NPs exhibited remarkable cytotoxic activities against breast adenocarcinoma (MCF-7) cells with IC<sub>50</sub> values of 44.87 ± 11.49, 23.3 ± 3.73, 23.88 ± 6.29, 17.98 ± 3.99, 18.69 ± 2.22, and 7.5 ± 0.69 µg/mL, respectively; as compared to free AA and OX (IC<sub>50</sub> of 150.80 ± 26.50 and 147.70 ± 63.91 µg/mL, respectively). Additionally, treatment of MCF-7 cells with IC<sub>50</sub> concentrations of AA, AA/CS NPs, AA/PEG-CS NPs, OX, OX/CS NPs, OX/PEG-CS NPs, AA-OX/CS NPs or AA-OX/PEG-CS NPs increased the percentages of early apoptotic cells to 5.28%, 9.53%, 11.20%, 5.27%, 13.80%, 8.43%, 2.32%, and 10.10%, respectively, and increased the percentages of late apoptotic cells to 0.98%, 0.37%, 2.41%, 2.06%, 0.97%, 9.66%, 56%, and 81.50%, respectively. These results clearly indicate that PEGylation enhances the apoptotic effect of AA and OX alone, in addition to potentiating the apoptotic effect of AA and OX when combined on MCF-7 cells. In conclusion, PEGylated chitosan nanoparticles encapsulating AA, OX, or AA and OX represent an effective formula for induction of apoptosis in MCF-7 cells.
The Lectin Domain of the Polypeptide GalNAc Transferase Family of Glycosyltransferases (ppGalNAc Ts) Acts as a Switch Directing Glycopeptide Substrate Glycosylation in an N- or C-terminal Direction, Further Controlling Mucin Type O-Glycosylation (2013)

Mucin type O-glycosylation is initiated by a large family of polypeptide GalNAc transferases (ppGalNAc Ts) that add α-GalNAc to the Ser and Thr residues of peptides. Of the 20 human isoforms, all but one are composed of two globular domains linked by a short flexible linker: a catalytic domain and a ricin-like lectin carbohydrate binding domain. Presently, the roles of the catalytic and lectin domains in peptide and glycopeptide recognition and specificity remain unclear. To systematically study the role of the lectin domain in ppGalNAc T glycopeptide substrate utilization, we have developed a series of novel random glycopeptide substrates containing a single GalNAc-O-Thr residue placed near either the N or C terminus of the glycopeptide substrate. Our results reveal that the presence and N- or C-terminal placement of the GalNAc-O-Thr can be important determinants of overall catalytic activity and specificity that differ between transferase isoforms. For example, ppGalNAc T1, T2, and T14 prefer C-terminally placed GalNAc-O-Thr, whereas ppGalNAc T3 and T6 prefer N-terminally placed GalNAc-O-Thr. Several transferase isoforms, ppGalNAc T5, T13, and T16, display equally enhanced N- or C-terminal activities relative to the nonglycosylated control peptides. This N- and/or C-terminal selectivity is presumably due to weak glycopeptide binding to the lectin domain, whose orientation relative to the catalytic domain is dynamic and isoform-dependent. Such N- or C-terminal glycopeptide selectivity provides an additional level of control or fidelity for the O-glycosylation of biologically significant sites and suggests that O-glycosylation may in some instances be exquisitely controlled.
Novel Cytokinin Derivatives Do Not Show Negative Effects on Root Growth and Proliferation in Submicromolar Range (2012)

Tetrahydropyranyl substitution at N9-position of cytokinin purine ring significantly enhances acropetal transport of a given cytokinins. Together with the methoxy-substitution, impedes accumulation of non-active cytokinin glucoside forms in roots, allows gradual release of the active base, and has a significant effect on the distribution and amount of endogenous isoprenoid cytokinins in different plant tissues. The utilization of novel aromatic cytokinin derivatives can distinctively improve expected hormonal effects in plant propagation techniques in the future.
Analysis of Radio Propagation in Co- and Cross-Polarization in Urban Environment (2008)

The behaviour of radio propagation in co- and cross-polarization in urban environment is studied with the aid of both ray tracing simulation and MIMO measurements. A ray tracing (RT) model including diffuse scattering has been adopted, therefore allowing the tuning of the RT model and the analysis of the role of diffuse scattering in cross-polarization propagation. A high degree of cross-polarization coupling is observed, especially in NLOS cases, confirming the feasibility of efficient and compact MIMO schemes adopting dual polarized antennas.
In vivo behavior of epoxy-crosslinked porcine heart valve cusps and walls (2000)

Calcification limits the long-term durability of xenograft glutaraldehyde-crosslinked heart valves. In this study, epoxy-crosslinked porcine aortic valve tissue was evaluated after subcutaneous implantation in weanling rats. Non-crosslinked valves and valves crosslinked with glutaraldehyde or carbodiimide functioned as control. Epoxy-crosslinked valves had somewhat lower shrinkage temperatures than the crosslinked controls, and within the series also some macroscopic and microscopic differences were obvious. After 8 weeks implantation, cusps from non-crosslinked valves were not retrieved. The matching walls were more degraded than the epoxy- and control-crosslinked walls. This was observed from the higher cellular ingrowth with fibroblasts, macrophages, and giant cells. Furthermore, non-crosslinked walls showed highest numbers of lymphocytes, which were most obvious in the capsules. Epoxy- and control-crosslinked cusps and walls induced lower reactions. Calcification, measured by von Kossa-staining and by Ca-analysis, was always observed. Crosslinked cusps calcified more than walls. Of all wall samples, the non-crosslinked walls showed the highest calcification. It is concluded that epoxy-crosslinked valve tissue induced a foreign body and calcification reaction similar to the two crosslinked controls. Therefore, epoxy-crosslinking does not represent a solution for the calcification problem of heart valve bioprostheses. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res (Appl Biomater) 53: 18–27, 2000
Interspecific exchange of avian influenza virus genes in Alaska: the influence of trans‐hemispheric migratory tendency and breeding ground sympatry (2010)

The movement and transmission of avian influenza viral strains via wild migratory birds may vary by host species as a result of migratory tendency and sympatry with other infected individuals. To examine the roles of host migratory tendency and species sympatry on the movement of Eurasian low-pathogenic avian influenza (LPAI) genes into North America, we characterized migratory patterns and LPAI viral genomic variation in mallards (Anas platyrhynchos) of Alaska in comparison with LPAI diversity of northern pintails (Anas acuta). A 50-year band-recovery data set suggests that unlike northern pintails, mallards rarely make trans-hemispheric migrations between Alaska and Eurasia. Concordantly, fewer (14.5%) of 62 LPAI isolates from mallards contained Eurasian gene segments compared to those from 97 northern pintails (35%), a species with greater inter-continental migratory tendency. Aerial survey and banding data suggest that mallards and northern pintails are largely sympatric throughout Alaska during the breeding season, promoting opportunities for interspecific transmission. Comparisons of full-genome isolates confirmed near-complete genetic homology (>99.5%) of seven viruses between mallards and northern pintails. This study found viral segments of Eurasian lineage at a higher frequency in mallards than previous studies, suggesting transmission from other avian species migrating inter-hemispherically or the common occurrence of endemic Alaskan viruses containing segments of Eurasian origin. We conclude that mallards are unlikely to transfer Asian-origin viruses directly to North America via Alaska but that they are likely infected with Asian-origin viruses via interspecific transfer from species with regular migrations to the Eastern Hemisphere.
Photoinduced Lattice Instability in SnSe (2021)

We report femtosecond optical pump and x-ray diffraction probe experiments on SnSe. We find that under photoexcitation, SnSe has an instability towards an orthorhombically-distorted rocksalt structure that is not present in the equilibrium phase diagram. The new lattice instability is accompanied by a drastic softening of the lowest frequency A$_g$ phonon which is usually associated with the thermodynamic Pnma-Cmcm transition. However, our reconstruction of the transient atomic displacements shows that instead of moving towards the Cmcm structure, the material moves towards a more symmetric orthorhombic distortion of the rock-salt structure belonging to the Immm space group. The experimental results combined with density functional theory (DFT) simulations show that photoexcitation can act as a state-selective perturbation of the electronic distribution, in this case by promoting electrons from Se 4$p$ Sn 5$s$ derived bands from deep below the Fermi level. The subsequent potential energy landscape modified by such electronic excitation can reveal minima with metastable phases that are distinct from those accessible in equilibrium. These results may have implications for optical control of the thermoelectric, ferroelectric and topological properties of the monochalcogenides and related materials.
Pyrido[3,4-e]-1,2,4-triazines and related heterocycles as potential antifungal agents (1989)

The preparation and biological activities of a series of pyrido[3,4-e]-1,2,4-triazines, 1,2,4-triazino[5,6-c]quinolines, and related fused triazines are described. Methyl, amino, and acylamino substituents were placed in the pyridyl ring of the former system. Other structural modifications included various alkyl, cycloalkyl, substituted phenyl, and heterocyclic groups in the 3-position of these ring systems. In agar dilution assays, actives in this series inhibited strains of Candida, Aspergillus, Mucor, and Trychophyton species at MIC's of less than or equal to 16 micrograms/mL.
N‐Cinnamoylation of Antimalarial Classics: Quinacrine Analogues with Decreased Toxicity and Dual‐Stage Activity (2013)

Abstract Plasmodium falciparum , the causative agent of the most lethal form of malaria, is becoming increasingly resistant to most available drugs. A convenient approach to combat parasite resistance is the development of analogues of classical antimalarial agents, appropriately modified in order to restore their relevance in antimalarial chemotherapy. Following this line of thought, the design, synthesis and in vitro evaluation of N ‐cinnamoylated quinacrine surrogates, 9‐( N ‐cinnamoylaminobutyl)‐amino‐6‐chloro‐2‐methoxyacridines, is reported. The compounds were found to be highly potent against both blood‐stage P. falciparum , chloroquine‐sensitive 3D7 (IC 50 =17.0–39.0 n M ) and chloroquine‐resistant W2 and Dd2 strains (IC 50 =3.2–41.2 and 27.1–131.0 n M , respectively), and liver‐stage P. berghei (IC 50 =1.6–4.9 μ M ) parasites. These findings bring new hope for the possible future “rise of a fallen angel” in antimalarial chemotherapy, with a potential resurgence of quinacrine‐related compounds as dual‐stage antimalarial leads.
PRODEEDINGS OF RIKEN BNL RESEARCH CENTER WORKSHOP : HIGH PERFORMANCE COMPUTING WITH QCDOC AND BLUEGENE. (2003)

Staff of Brookhaven National Laboratory, Columbia University, IBM and the RIKEN BNL Research Center organized a one-day workshop held on February 28, 2003 at Brookhaven to promote the following goals: (1) To explore areas other than QCD applications where the QCDOC and BlueGene/L machines can be applied to good advantage, (2) To identify areas where collaboration among the sponsoring institutions can be fruitful, and (3) To expose scientists to the emerging software architecture. This workshop grew out of an informal visit last fall by BNL staff to the IBM Thomas J. Watson Research Center that resulted in a continuing dialog among participants on issues common to these two related supercomputers. The workshop was divided into three sessions, addressing the hardware and software status of each system, prospective applications, and future directions.
Absorption and fate of BAY MKH 6561 in jointed goatgrass and downy brome (2001)

To be effective, postemergence herbicides must be absorbed and translocated to sites of action in proper form and quantity. Any factor that interferes in this process may account for differential sensitivity. Adjuvant effects on foliar absorption of BAY MKH 6561 by jointed goatgrass and downy brome were evaluated under growth chamber conditions. Absorption of BAY MKH 6561 by jointed goatgrass and downy brome without adjuvants was 41 and 30% of applied, respectively, 48 h after treatment (HAT). Herbicide absorption with methylated seed oil (MSO) was significantly higher than with nonionic surfactant (NIS) 24 and 48 HAT. The addition of urea ammonium nitrate (UAN) to MSO and NIS significantly increased absorption over MSO and NIS alone 24 HAT, but absorption was similar to that obtained with MSO 48 HAT. Averaged across adjuvant combinations, jointed goatgrass and downy brome absorbed 90 and 89% of applied BAY MKH 6561, respectively, 48 HAT. BAY MKH 6561 translocation and metabolism in jointed goatgrass, downy brome, and winter wheat were also evaluated. More 14C-BAY MKH 6561 translocated to shoot and root tissue in downy brome than in jointed goatgrass and winter wheat. Root exudation accounted for 26% of root-translocated BAY MKH 6561 in jointed goatgrass, 31% in downy brome, and 43% in winter wheat. Winter wheat, jointed goatgrass, and downy brome metabolized 82, 65, and 50% of absorbed 14C-BAY MKH 6561 12 HAT, respectively, and 97% metabolism occurred in all species 48 HAT. Exponential decay equations predicted a 7-h BAY MKH 6561 half-life in winter wheat, 10-h half-life in jointed goatgrass, and 13-h half-life in downy brome. Jointed goatgrass absorbed amounts of 14C-BAY MKH 6561 that were similar to those absorbed by downy brome, but jointed goatgrass was intermediate in translocation and metabolism compared to winter wheat and downy brome. Therefore, differential translocation and metabolism may explain differential field susceptibility observed between winter wheat, jointed goatgrass, and downy brome.
Extraction of time constants ratio over nine orders of magnitude for understanding random telegraph noise in metal–oxide–semiconductor field-effect transistors (2014)

The random telegraph noise (RTN) characteristics in numerous metal–oxide–semiconductor field-effect transistors were evaluated accurately with small floor noise of 59 µV. Because of the small floor noise RTN characteristics with small amplitudes could be measured. The time constants: time to emission (τ e ) and time to capture (τ c ) were extracted from measurement results with sampling period of 1 µs and sampling time of 600 s, and they were distributed for over six orders of magnitude. Based on the extracted data of τ e and τ c , there is no correlation between <?CDATA $\langle \tau _{\text{e}}\rangle $?> and <?CDATA $\langle \tau _{\text{c}}\rangle $?> . Also, it was clarified that the time constant ratio ( <?CDATA $\langle \tau _{\text{c}}\rangle /\langle \tau _{\text{e}}\rangle $?> ) were distributed over nine orders of magnitude. Additionally, the gate bias dependence of <?CDATA $\langle \tau _{\text{e}}\rangle $?> , <?CDATA $\langle \tau _{\text{c}}\rangle $?> , and <?CDATA $\langle \tau _{\text{c}}\rangle /\langle \tau _{\text{e}}\rangle $?> were analyzed. The distribution of <?CDATA $\langle \tau _{\text{e}}\rangle $?> is shifted to larger values with the increase of drain current ( I D ) and that of <?CDATA $\langle \tau _{\text{c}}\rangle $?> is shifted to smaller values with the increase of I D .
AVXS-101 Phase 1 Gene Replacement Therapy Clinical Trial in SMA Type 1: Continued Independence from Nutritional and Ventilatory Support in Patients Dosed Early in Disease Progression (S29.003) (2018)

Here we report clinical data of Spinal muscular atrophy Type 1 (SMA1) infants treated with a one-time intravenous dose of the proposed therapeutic dose of AVXS-101, a gene replacement therapy that crosses the blood-brain-barrier.
Modularized instrument system for turbojet engine test facilities (1972)

A modular instrument system is being developed to handle the many data channels encountered in turbojet engine testing. Each module contains a group of transducers and all the signal conditioning multiplexing, and digitizing electronics necessary for direct interface with a digital computer. The digital interface within each module is the same for all modules; in addition, each module provides a controlled environment for its contents. A minicomputer in the control room gathers the data, performs on-line calculation and display, and interfaces with a shared recording and computing system. The advantages of this system are: (1) reduced manpower for system installation, setup, and checkout; (2) standardized equipment interfaces; (3) increased reliability through automatic system testing and minimization of manual adjustments; and (4) reduced cost through minimization of wiring and simplification of control room display.
An integration of all refractory Josephson logic LSI circuit (1985)

An integration process for the fabrication of an all refractory Josephson LSI logic circuit is described. In this process, niobium nitride and niobium double-layered Josephson junctions were integrated using a reactive ion etching with a 2.5 μm minimum feature. A highly selective and anisotropic RIE process and a planarizing technology have been developed for intagrating a circuit with LSI complexity. For evaluating the process capability, test vehicle circuits with MSI/LSI level complexity have been designed and fabricated using this process. An 8 bit ripple carry adder and a 4×4 bit parallel multiplier have been integrated with Josephson four junction logic ( 4JL ) gates, the largest of which contains more than 2800 Josephson junctions. Both functionality and high-speed performance testings have been successfully performed with these test circuits.