gebhart/patrepeval huggingface dataset:
Molecular basis of tail-anchored integral membrane protein recognition by the cochaperone Sgt2 (2021)

The targeting and insertion of tail-anchored (TA) integral membrane proteins (IMPs) into the correct membrane is critical for cellular homeostasis. The fungal protein Sgt2, and its human homolog SGTA, is the entry point for clients to the guided entry of tail-anchored protein (GET) pathway, which targets endoplasmic reticulum-bound TA IMPs. Consisting of three structurally independent domains, the C terminus of Sgt2 binds to the hydrophobic transmembrane domain (TMD) of clients. However, the exact binding interface within Sgt2 and molecular details that underlie its binding mechanism and client preference are not known. Here, we reveal the mechanism of Sgt2 binding to hydrophobic clients, including TA IMPs. Through sequence analysis, biophysical characterization, and a series of capture assays, we establish that the Sgt2 C-terminal domain is flexible but conserved and sufficient for client binding. A molecular model for this domain reveals a helical hand forming a hydrophobic groove approximately 15 Å long that is consistent with our observed higher affinity for client TMDs with a hydrophobic face and a minimal length of 11 residues. This work places Sgt2 into a broader family of TPR-containing cochaperone proteins, demonstrating structural and sequence-based similarities to the DP domains in the yeast Hsp90 and Hsp70 coordinating protein, Sti1.
Antineoplastic Agents. 590. X-ray Crystal Structure of Dolastatin 16 and Syntheses of the Dolamethylleuine and Dolaphenvaline Units (2011)

Three advances necessary to bring dolastatin 16 (1) into full-scale preclinical development as an anticancer drug have been accomplished. The X-ray crystal structure of dolastatin 16 has been solved, which allowed stereoselective syntheses of its two new amino acid units, dolamethylleuine (Dml) and dolaphenvaline (Dpv), to be completed. The X-ray crystal structures of synthetic Z-Dml and TFA-Dpv have also been completed.
Fully depleted devices for designers: FDSOI and FinFETs (2012)

Technologies featuring fully depleted transistors are entering the mainstream for designs at the 28nm, 20nm, and 14nm nodes. Although these devices have been the playground of device engineers for more than a decade it is for the most part only recently that they have been introduced to circuit designers and logic chip integrators. The physical structure and many of the features - or lack thereof - of the transistors vis-à-vis conventional planar devices are different, opening some new doors and perhaps closing some old ones. In this paper we discuss both planar (variously called ETSOI/UTBB/FDSOI <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">1</sup> ) and three-dimensional (variously called FinFET or trigate or doublegate) fully depleted devices, comparing and contrasting them with one another and with classical devices, and in both bulk and SOI manifestations.
Abstract 4031: Different expression of programmed death 1 (PD1) and its ligand (PD-L1) in esophageal and gastric cancer (2016)

Abstract Background: Prognosis of gastric and esophageal cancer remains poor. Improvements in gastric and esophageal cancer treatments are urgently needed. Programmed cell death 1 receptor (PD1) and its ligand 1 (PD-L1) are known to interact with T cells promoting epithelial cancer tolerance. Several therapeutic monoclonal antibodies blocking this interaction are reaching the clinical praxis. Therefore it is relevant to investigate the role of these biomarkers in different types of malignancy. Methods: Four different copies of tissue microarrays (TMA), each including healthy mucosa (n = 74) and a total of 241 clinically annotated malignancies of the esophagus (n = 80) and stomach (n = 161) were constructed and stained with PD1, PD-L1, and CD8 specific reagents. Results: Interestingly, only two cancer samples out of the 241 specimens investigated weakly expressed PD-L1. None of the normal mucosa epithelial cells expressed PD-L1. Stromal PD1 expression correlated with infiltration by CD8+ lymphocytes (rho = 0.4; P&amp;lt;0.0001). Elevated intraepithelial presence of CD8+ and/or PD1+ cells in gastric cancer was significantly correlated with longer patients’ survival. No correlation could be found in esophageal cancer. Conclusion: In contrast to other epithelial cancers, PD-L1 expression was virtually absent in the investigated malignancies of the esophagus and stomach. PD1 expression in the stroma surrounding such malignancies correlated with intraepithelial presence of T-cells CD8+ expression, and with better prognosis in gastric cancer patients. Citation Format: Silvio Däster, Serenella Eppenberger-Castori, Raoul A. Droeser, Hannah M. Schaefer, Giulio C. Spagnoli, Luigi Terracciano, Luigi Tornillo, Urs von Holzen. Different expression of programmed death 1 (PD1) and its ligand (PD-L1) in esophageal and gastric cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4031.
Pharmacokinetics of retinal drug delivery (2019)

Abstract The Sight threatening changes of many ophthalmic diseases are present in the retina. Thus, retina is an important drug target, but it is not an easy tissue for drug delivery. Depending on the route of drug delivery (intravitreal, periocular, systemic) the retinal drug exposure is hampered by various physical barriers (vitreous, inner limiting membrane, retinal pigment epithelium and retinal capillaries) and blood flow factors. In this presentation, delivery aspects are discussed quantitatively utilizing modeling tools and addressing required dosing in different situations. Intravitreal, periocular and systemic routes of drug delivery will be discussed. Furthermore, scaling factors for drug doses between mouse, rabbit and humans are presented.
Impact of blind versus non-blind channel estimation on the BER performance of GSM receivers (2002)

We investigate in this paper whether the HOS-based blind channel estimation method EVI (eigenvector approach to blind identification) can compete with the nonblind cross-correlation-based scheme used in state-of-the-art GSM receivers (Global System for Mobile communication). For blind, non-blind, and ideal estimates of COST-207 mobile radio channels, we give simulated bit error rates (BER) after Viterbi detection in terms of the mean signal-to-noise ratio (SNR). Averaged over three COST-207 propagation environments, EVI leads to a mean SNR loss of 1.2 dB only, while it saves the 22% overhead in the GSM data rate due to the transmission of training sequences. Since just 142 samples are used for channel estimation, we consider this performance outstanding for an approach based on HOS.
Non Thermal Plasma Recovery of Hydrogen from Sabatier Waste Methane (2011)

Hydrogen recovery from various waste streams within constrained life support systems such as that aboard the International Space Station is of particular interest for improved overall mass utilization. Using non-thermal plasma in combination with a metal catalyst, recoverable hydrogen was generated from a methane-carbon dioxide gas stream similar to that discharged from a Sabatier methanation reactor. Improved methane conversion and hydrogen recovery was demonstrated by testing a variety of reactor and catalyst configurations. An overall understanding of the basic plasma-catalyst interaction will facilitate further development geared towards implementation of the non-thermal plasma hydrogen reclamation system with the rest of the cabin atmosphere revitalization systems for oxygen and water recovery.
P1‐403: Trans‐cortical correlations of pittsburgh compound‐B in cognitively normal elderly, MCI and Alzheimer's: Implications for the natural history of amyloid deposition (2010)

Correlations between amyloid deposition and glucose metabolism across distinct subcortical and cortical regions of AD patients have been shown, suggesting distant sequelae of local amyloid deposition. However, because PiB retention across some brain regions are correlated this interpretation could be complicated. Determine trans-cortical correlations of amyloid deposition in amyloid-positive normal control subjects, mild cognitive impairment (MCI) and AD patients. PiB PET scans from 88 consecutive amyloid-positive subjects were analyzed; 22 controls (56-80yrs), 24 MCI patients (65-82yrs) and 42 AD patients (56-94yrs). Regional PiB retention measures (SUVR: cerebellum reference) were determined and atrophy-corrected using an MR-based method. PiB retention was compared across cortical regions using Pearson's correlations and corrected for multiple comparisons using the False-Discovery Rate method. In all subjects with amyloid deposition, we observed local positive correlations within frontal, posterior (precuneus, parietal, temporal) and occipital cortices. In controls with amyloid deposition, we also observed weaker trans-cortical correlations between frontal and posterior regions. In MCI, the frontal-posterior correlations were much stronger and there were some occipital-posterior correlations. In AD, all of these correlations were stronger and some moderately strong correlations appeared between occipital and frontal regions. In AD there were no correlations between mesial temporal cortex and other cortical regions, while in MCI and control subjects these correlations were apparent and more marked, especially in MCI. The associations of amyloid deposition between cortical regions may vary with increasing cognitive (and presumably pathological) severity. Our findings suggest that the early phases of amyloid deposition are varied across the cortex and that the occipital cortex may be the last cortical region to develop heavy amyloid deposition. The weaker correlations of PiB retention in mesial temporal areas with those in other cortical areas with increasing disease severity may be due to increasing atrophy in this region.
Seasonal fluctuations in ionic concentrations drive microbial succession in a hypersaline lake community (2013)

Microbial community succession was examined over a two-year period using spatially and temporally coordinated water chemistry measurements, metagenomic sequencing, phylogenetic binning and de novo metagenomic assembly in the extreme hypersaline habitat of Lake Tyrrell, Victoria, Australia. Relative abundances of Haloquadratum-related sequences were positively correlated with co-varying concentrations of potassium, magnesium and sulfate, but not sodium, chloride or calcium ions, while relative abundances of Halorubrum, Haloarcula, Halonotius, Halobaculum and Salinibacter-related sequences correlated negatively with Haloquadratum and these same ionic factors. Nanohaloarchaea and Halorhabdus-related sequence abundances were inversely correlated with each other, but not other taxonomic groups. These data, along with predicted gene functions from nearly-complete assembled population metagenomes, suggest different ecological phenotypes for Nanohaloarchaea and Halorhabdus-related strains versus other community members. Nucleotide percent G+C compositions were consistently lower in community metagenomic reads from summer versus winter samples. The same seasonal G+C trends were observed within taxonomically binned read subsets from each of seven different genus-level archaeal groups. Relative seasonal abundances were also linked to percent G+C for assembled population genomes. Together, these data suggest that extreme ionic conditions may exert selective pressure on archaeal populations at the level of genomic nucleotide composition, thus contributing to seasonal successional processes. Despite the unavailability of cultured representatives for most of the organisms identified in this study, effective coordination of physical and biological measurements has enabled discovery and quantification of unexpected taxon-specific, environmentally mediated factors influencing microbial community structure.
Microarray Analysis of p53 Target Gene Expression Patterns in the Spleen and Thymus in Response to Ionizing Radiation (2003)

The ability of p53 to induce apoptosis through transactivation of its target genes is critical for its function as a tumor suppressor. To identify the critical p53 target genes that mediate apoptosis through these pathways, we examined p53-dependent apoptosis in vivo where these apoptotic pathways are intact. p53 wild-type and null animals were irradiated and the global p53 gene expression patterns in response to ionizing radiation were examined in two tissues (spleen and thymus) which undergo p53-dependent apoptosis in response to ionizing radiation. We found that the vast majority of genes that increased or decreased in a p53-dependent manner did so in a tissue specific manner. Although the spleen and thymus had similar levels of p53-dependent apoptosis after ionizing radiation, there was very little overlap in the induced or repressed targets. This suggested that distinct targets may mediate apoptosis in these tissues. In addition, these microarray analyses also led to the identification of several novel p53 targets. Several of these targets appear to be involved in known p53 functions such as the induction of apoptosis (bim) or the initiation of DNA repair (DinB). However, some p53 targets (both confirmed and unconfirmed) link p53 to the anti-tumor immune response (MIP 1-alpha). Further characterization of the tissue specific mediators of p53-dependent responses will greatly increase our understanding of p53 function.
Reaction of organotin hydrides with acid chlorides. Mechanism of aldehyde and ester formation (1984)

Tri-n-butyltin hydride reacts with acid chloride, RCOCl, spontaneously at ambient temperatures to form n-Bu 3SnCl, RCHO, RC(O)OCH 2R, and a number of minor products. The reaction is not a radical chain process, nor are radicals involved as intermediates. The initial products are n-Bu 3SnCl and RCHO; it is not known whether these are formed in a direct reaction between n-Bu 3SnH and RCOCl or via an unstable chloroalkoxytin species, n-Bu 3SnOCHClR. The remaining products are formed by subsequent reactions of the aldehyde. Thus, the alkoxytin species, n-Bu 3SnOCH 2R, is formed from aldehyde and tin hydride. This can react further with RCOCl to form the ester RC(O)OCH 2R, with RCHO to form n-Bu 3SnOCH(R)OCH 2R, and with n-Bu 3SnH to form RCH 2OH. The aldehyde can also react with RCOCl to form the α′-chloro ester, RC(O)OCHClR.
Reflective masks for extreme ultraviolet lithography (1994)

Extreme ultraviolet lithographic masks are made by patterning multilayer reflective coatings with high normal incidence reflectivity. Masks can be patterned by depositing a patterned absorber layer above the coating or by etching the pattern directly into the coating itself. Electromagnetic simulations showed that absorber-overlayer masks have superior imaging characteristics over etched masks (less sensitive to incident angles and pattern profiles). In an EUVL absorber overlayer mask, defects can occur in the mask substrate, reflective coating, and absorber pattern. Electromagnetic simulations showed that substrate defects cause the most severe image degradation. A printability study of substrate defects for absorber overlayer masks showed that printability of 25 nm high substrate defects are comparable to defects in optical lithography. Simulations also indicated that the manner in which the defects are covered by multilayer reflective coatings can affect printability. Coverage profiles that result in large lateral spreading of defect geometries amplify the printability of the defects by increasing their effective sizes. Coverage profiles of Mo/Si coatings deposited above defects were studied by atomic force microscopy and TEM. Results showed that lateral spread of defect geometry is proportional to height. Undercut at defect also increases the lateral spread. Reductions in defect heights were observed for 0.15 μm wide defect lines. A long-term study of Mo/Si coating reflectivity revealed that Mo/Si coatings with Mo as the top layer suffer significant reductions in reflectivity over time due to oxidation.
Detection of Poly- and Perfluoroalkyl Substances (PFASs) in U.S. Drinking Water Linked to Industrial Sites, Military Fire Training Areas, and Wastewater Treatment Plants (2016)

Drinking water contamination with poly- and perfluoroalkyl substances (PFASs) poses risks to the developmental, immune, metabolic, and endocrine health of consumers. We present a spatial analysis of 2013-2015 national drinking water PFAS concentrations from the U.S. Environmental Protection Agency's (US EPA) third Unregulated Contaminant Monitoring Rule (UCMR3) program. The number of industrial sites that manufacture or use these compounds, the number of military fire training areas, and the number of wastewater treatment plants are all significant predictors of PFAS detection frequencies and concentrations in public water supplies. Among samples with detectable PFAS levels, each additional military site within a watershed's eight-digit hydrologic unit is associated with a 20% increase in PFHxS, a 10% increase in both PFHpA and PFOA, and a 35% increase in PFOS. The number of civilian airports with personnel trained in the use of aqueous film-forming foams is significantly associated with the detection of PFASs above the minimal reporting level. We find drinking water supplies for 6 million U.S. residents exceed US EPA's lifetime health advisory (70 ng/L) for PFOS and PFOA. Lower analytical reporting limits and additional sampling of smaller utilities serving <10000 individuals and private wells would greatly assist in further identifying PFAS contamination sources.
Phosphorylation State-Dependent High Throughput Screening of the c-Met Kinase (2010)

High-throughput screening (HTS) of ~50,000 chemical compounds against phosphorylated and unphosphorylated c-Met, a tyrosine kinase receptor for hepatocyte growth factor (HGF), was carried out in order to compare hit rates, hit potencies and also to explore scaffolds that might serve as potential leads targeting only the unphosphorylated form of the enzyme. The hit rate and potency for the confirmed hit molecules were higher for the unphosphoryalted form of c-Met. While the target of small molecule inhibitor discovery efforts has traditionally been the phosphorylated form, there are now examples of small molecules that target unphosphorylated kinases. Screening for inhibitors of unphosphorylated kinases may represent a complementary approach for prioritizing chemical scaffolds for hit-to-lead follow ups.
Molecular Requirements for RNA-induced Silencing Complex Assembly in the Drosophila RNA Interference Pathway (2005)

Complexes in the Drosophila RNA-induced silencing complex (RISC) assembly pathway can be resolved using native gel electrophoresis, revealing an initiator called R1, an intermediate called R2, and an effector called R3 (now referred to as holo-RISC). Here we show that R1 forms when the Dicer-2/R2D2 heterodimer binds short interfering RNA (siRNA) duplexes. The heterodimer alone can initiate RISC assembly, indicating that other factors are dispensable for initiation. During assembly, R2 requires Argonaute 2 to convert into holo-RISC. This requirement is reminiscent of the RISC-loading complex, which also requires Argonaute 2 for assembly into RISC. We have compared R2 to the RISC-loading complex and show that the two complexes are similar in their sensitivities to ATP and to chemical modifications on siRNA duplexes, indicating that they are likely to be identical. We have examined the requirements for RISC formation and show that the siRNA 5'-termini are repeatedly monitored during RISC assembly, first by the Dcr-2/R2D2 heterodimer and again after R2 formation, before siRNA unwinding. The 2'-position of the 5'-terminal nucleotide also affects RISC assembly, because an siRNA strand bearing a 2'-deoxyribose at this position can inhibit the cognate strand from entering holo-RISC; in contrast, the 2'-deoxyribose-modified strand has enhanced activity in the RNA interference pathway.
Possible high-pressure orbital quantum criticality and an emergent resistive phase in PbRuO3 (2013)

The orbital ordering transition in the metallic perovskite PbRuO${}_{3}$ is suppressed from 90 K at ambient pressure towards zero temperature at 50 kbar, where non-Fermi liquid resistivity with a temperature exponent $n$ $=$ 1.6 is observed. This evidences a possible quantum critical point brought about by orbital fluctuations, rather than spin fluctuations as observed in Sr${}_{3}$Ru${}_{2}$O${}_{7}$ and heavy fermion conductors. An anomalous increase of resistivity is observed at pressures above \ensuremath{\sim}100 kbar, and a transition to a more resistive, possibly semiconducting, phase is observed at 300 kbar and ambient temperature.
Conjugated polyelectrolyte (CPE) poly[3-[6-(N-methylimidazolium)hexyl]-2,5-thiophene] complexed with aqueous sodium dodecylsulfate amphiphile: synthesis, solution structure and “surfactochromic” properties (2011)

We report on the synthesis, solution structure and photophysical properties of poly[3-[6-(N-methylimidazolium)hexyl]-2,5-thiophene] bromide (P3ImiHT) when complexed with sodium dodecylsulfate (SDS). Synthesis of P3ImiHT used a Grignard metathesis (GRIM)-type route developed by McCullough, followed by quaternisation of the bromohexyl side groups of poly[3-(6-bromohexyl)thiophene] with N-methylimidazole. P3ImiHT was mixed with either SDS or deuterated SDS to form the P3ImiHT(SDS)x complex, where x is the molar ratio of surfactant to polyelectrolyte repeat unit, in D2O and studied using small-angle neutron scattering (SANS) and optical spectroscopy. Marked differences in behaviour are observed upon interaction of P3ImiHT with SDS compared with the related poly[3-(6-trimethylammoniumhexyl)thiophene] bromide (P3TMAHT). At room temperature, P3ImiHT forms charged aggregates with electrostatic repulsion which are eliminated by the SDS addition. For x ≤ 1 P3ImiHT and SDS are molecularly mixed and form ellipsoidal (x = 1/5) or sheet-like (x = 1/2–1) P3ImiHT(SDS)x aggregates. No visible precipitation is observed around the nominal charge compensation point (x = 1). For x > 1, P3ImiHT(SDS)x aggregates coexist with SDS rich micelles which turn from thick rod-like (x = 3/2) to non-charged (x = 2) and charged ellipsoidal micelles (x = 5). This transition is driven by decreasing free ion fraction. For x = 5, P3ImiHT(SDS)x forms a lamellar phase with a periodicity of ∼270 Å. The structural transitions are accompanied by an initial red-shift from 422 nm (x = 0) to 459 nm (x = 1), followed by a reverse blue-shift to 400 nm (x = 5) of the UV/vis absorption maxima. The photoexcitation spectra follow this trend but are ∼50 nm red-shifted, thus indicating energy transfer within the density of states after photoexcitation. The photoluminescence maximum is gradually blue-shifted from 643 nm to 597 nm on increasing x from 0 to 5, indicating a decrease in polymer–polymer interactions.
Design Principle and Static Coding Efficiency of STT-Coder: A Table-Driven Arithmetic Coder (2013)

We have proposed the concept of simple and fast binary arithmetic coder, STT-coder, in which arithmetic operation can be executed by referring a state transition table just like the case of Huffman coding. In our previous study, STT-coder with 3-bit interval register was designed and evaluated. Its coding efficiency was found to be satisfactory despite of the introduction of the simplification of the process. Then we have been trying to extend the register to 6-bit length in order to improve the performance of higher MPS probability sources. In this paper, we introduce a coding parameter of STT-coder, which is called as offset, and optimize the value to maximize the average coding efficiency. We further tried to enlarge the expected interval size after the renormalization to improve the coding efficiency of higher MPS probability sources by sacrificing the accuracy of interval division ratio in low MPS probability sources, which turned out to improve the coding efficiency in total. 