gebhart/patrepeval huggingface dataset:
Inhibition of IGF-1 receptor and alternate cancer targets by nordihydroguaiaretic acid (NDGA) analogs (2007)

LB-298 NDGA is a lignan isolated from the resinous extract of the creosote bush Larrea divaricata previously investigated as an anti-cancer agent. Numerous reports document the ability of NDGA to inhibit the growth of cancer cell lines in culture and in vivo, and NDGA is currently being investigated in a Phase 1 trial of prostate cancer patients at UCSF. The mechanisms whereby NDGA exerts its effects remain unclear, as numerous enzyme targets and diverse cellular effects have been reported. Previously, we demonstrated that NDGA directly inhibits the IGF-1 receptor (IGF-1R) and the c-erbB2/HER2/neu receptor in vitro, and that its ability to inhibit growth of breast cancer cells in culture and in vivo was associated with a blockade of these signaling pathways. Herein we pursue the hypothesis that the structure of nordihydroguaiaretic acid (NDGA) can be refined for selective potency against the insulin-like growth factor 1 receptor (IGF-1R) as a potential therapeutic target for breast cancer while diminishing its action against other cellular targets. Thus, a set of 8 NDGA analogs was prepared and examined for inhibitory potency against several reported targets of NDGA that could contribute to anti-cancer activity. Purified kinase domain peptides were employed to study the efficacy of these analogs at inhibiting the IGF-1R, HER2, and PDGFR tyrosine kinases. Activity against 15-lipoxygenase (15 LOX) and fatty acid synthase (FAS) was also determined in cell free assays. The anti-cancer effects of these compounds were determined by their ability to inhibit growth of MCF-7 breast cancer cells. The design of the analogs was based upon a cursory Topliss approach in which one of NDGA’s aromatic rings was modified with various substituents. Structural modification of one of the two catechol rings of NDGA was found to have little effect upon the inhibitory potency against both kinase activity of the IGF-1R and IGF-1 mediated cell growth of MCF-7 cells. 15-LOX was found to be most sensitive to structural modifications of NDGA. From the limited series of NDGA analogs examined, one cyclic compound with a framework similar to a natural product isolated from Larrea divaricata exhibited the greatest selectivity for IGF-1 mediated growth compared to inhibition of alternate targets such as 15-LOX and PDGFR. The results for this compound are significant because of its greater specificity towards the breast cancer target IGF-1R, less ubiquitous activity against general RTKs, and, importantly, a 10-fold weaker potency against 15-LOX, an enzyme which has a purported tumor suppressing role in breast cancer. With increased specificity and potency, synthetic analogs of NDGA may serve as new leads in developing novel therapeutic agents for breast and other cancers.
CoolMPS for robust sequencing of single-nuclear RNAs captured by droplet-based method (2020)

Massively-parallel single-cell and single-nucleus RNA sequencing (scRNA-seq, snRNA-seq) requires extensive sequencing to achieve proper per-cell coverage, making sequencing resources and availability of sequencers critical factors for conducting deep transcriptional profiling. CoolMPS is a novel sequencing-by-synthesis approach that relies on nucleotide labeling by re-usable antibodies, but whether it is applicable to snRNA-seq has not been tested. Here, we use a low-cost and off-the-shelf protocol to chemically convert libraries generated with the widely-used Chromium 10X technology to be sequenceable with CoolMPS technology. To assess the quality and performance of converted libraries sequenced with CoolMPS, we generated a snRNA-seq dataset from the hippocampus of young and old mice. Native libraries were sequenced on an Illumina Novaseq and libraries that were converted to be compatible with CoolMPS were sequenced on a DNBSEQ-400RS. CoolMPS-derived data faithfully replicated key characteristics of the native library dataset, including correct estimation of ambient RNA-contamination, detection of captured cells, cell clustering results, spatial marker gene expression, inter- and intra-replicate differences and gene expression changes during aging. In conclusion, our results show that CoolMPS provides a viable alternative to standard sequencing of RNA from droplet-based libraries.
Impact of Thermal Annealing on the Semicrystalline Nanomorphology of Spin-Coated Thin Films of Regioregular Poly(3-alkylthiophene)s as Observed by High-Resolution Transmission Electron Microscopy and Grazing Incidence X-ray Diffraction (2012)

The impact of thermal annealing on the growth of crystalline nanodomains of poly(3-alkylthiophene) (P3AT) in thin films (15–20 nm thick) was investigated as a function of length of alkyl side chain by combined low-dose high-resolution transmission electron microscopy (HR-TEM) and grazing incidence X-ray diffraction (GIXD). Statistical analysis of the data yields the characteristic dimensions of the face-on oriented P3AT nanocrystals, i.e., average stem length lc along backbones and lateral dimension perpendicular to the stems la along side chains. The following trends were identified: (i) in as-spin-coated films, the proportion of face-on oriented nanocrystals increases with the number of carbon atoms in the side chain, (ii) annealing favors the lateral in-plane growth of the nanocrystals along the side chain direction (aP3AT axis), (iii) for a given P3AT, the proportion of face-on oriented domains increases with annealing temperature, (iv) lateral growth along the aP3AT axis is most efficient for the longer octyl side chains, and (v) thermal annealing induces only modest lamellar thickening which is limited by the poor slide diffusion of π-stacked P3AT chains as opposed to lateral growth favored by weak van der Waals interactions between layers of n-alkyl side chains. The increase in the population of face-on oriented crystallites, observed when the length of the side chain increases, coincides with a corresponding decrease in the field effect mobility in annealed P3AT thin films.
Approaches to Overcome the Resolution Problem in Incoherent Digital Holography (2012)

Introduction Digital Incoherent Protected Correlation Holograms Off-Axis Optical Scanning Holography Synthetic Aperture with Fresnel Elements Summary Acknowledgments References
N-atom collective-state atomic interferometer with ultrahigh Compton frequency and ultrashort de Broglie wavelength, withNreduction in fringe width (2015)

We describe a collective-state atomic interferometer (COSAIN) with the signal fringe as a function of phase difference or rotation narrowed by $\sqrt{N}$ compared to a conventional interferometer, $N$ being the number of atoms, without entanglement. This effect arises from the interferences among collective states, and is a manifestation of interference at a Compton frequency of $10\phantom{\rule{0.16em}{0ex}}\ifmmode\times\else\texttimes\fi{}\phantom{\rule{0.16em}{0ex}}{10}^{30}$ Hz, or a de Broglie wavelength of 4.5 femtometer, for $N={10}^{6}$ and $v=1$ m/s. The population of the collective state of interest is detected by a null measurement scheme, in which an event corresponding to detection of zero photons corresponds to the system being in that particular collective state. The signal is detected by collecting fluorescence through stimulated Raman scattering of Stokes photons, which are emitted predominantly against the direction of the probe beam, for a high enough resonant optical density. The sensitivity of the ideal COSAIN is found to be given by the standard quantum limit. However, when detection efficiency and collection efficiency are taken into account, the detection scheme of the COSAIN increases the quantum efficiency of detection significantly in comparison to a typical conventional Raman atomic interferometer employing fluorescence detection, yielding a net improvement in stability by as much as a factor of 10. We discuss how the inhomogeneities arising from the nonuniformity in experimental parameters affect the COSAIN signal. We also describe an alternate experimental scheme to enhance resonant optical density in a COSAIN by using cross-linearly polarized counterpropagating Raman beams.
Supplementary Figure 5 from Polycomb CBX7 Promotes Initiation of Heritable Repression of Genes Frequently Silenced with Cancer-Specific DNA Hypermethylation (2023)

Supplementary Figure 5 from Polycomb CBX7 Promotes Initiation of Heritable Repression of Genes Frequently Silenced with Cancer-Specific DNA Hypermethylation
Representing information with computational resource bounds (2002)

A general framework for data compression, is which computational resource bounds are introduced at both the encoding and decoding end, is presented. We move away from Shannon's (1948) traditional communication system by introducing some structure at the decoder and model it by a Turing machine with finite computational resources. Information is measured using the resource bounded Kolmogorov (1965) complexity. In this setting, we investigate the design of efficient lossy encoders.
Bait Evaluation Methods for Urban Pest Management (2013)

Baits are a preferred type of formulation used in urban pest management, especially for the control of cockroaches, ants, and increasingly termites. With precise placement in areas away from contact with human population, especially children, and a reduced rate of active ingredient (AI) application in a given structure area, baits are more economical and pose less risk for consumers and the environment than other formulations. However, baits are very difficult to evaluate for efficacy. For baits, pest acceptance and horizontal transfer of bait are essential in order to control pest populations.
Shedding of Infectious SARS-CoV-2 Despite Vaccination (2021)

Abstract The SARS-CoV-2 Delta Variant of Concern is highly transmissible and contains mutations that confer partial immune escape. The emergence of Delta in North America caused the first surge in COVID-19 cases after SARS-CoV-2 vaccines became widely available. To determine whether individuals infected despite vaccination might be capable of transmitting SARS-CoV-2, we compared RT-PCR cycle threshold (Ct) data from 20,431 test-positive anterior nasal swab specimens from fully vaccinated (n = 9,347) or unvaccinated (n=11,084) individuals tested at a single commercial laboratory during the interval 28 June – 1 December 2021 when Delta variants were predominant. We observed no significant effect of vaccine status alone on Ct value, nor when controlling for vaccine product or sex. Testing a subset of low-Ct (&lt;25) samples, we detected infectious virus at similar rates, and at similar titers, in specimens from vaccinated and unvaccinated individuals. These data indicate that vaccinated individuals infected with Delta variants are capable of shedding infectious SARS-CoV-2 and could play a role in spreading COVID-19.
Kinetics and durability of transgene expression after intrastriatal injection of AAV9 vectors (2022)

Understanding the kinetics and durability of AAV-mediated transgene expression in the brain is essential for conducting basic neuroscience studies as well as for developing gene therapy approaches for CNS diseases. Here, we characterize and compare the temporal profile of transgene expression after bilateral injections into the mouse striatum of rAAV9 encoding GFP under the control of either a ubiquitous promoter (CAG), or the neuron-specific human synapsin (hSyn) and CamKII promoters. GFP protein expression with the CAG promoter was highest at 3 weeks, and then decreased to stable levels at 3 and 6 months. Surprisingly, GFP mRNA levels continued to increase from 3 weeks to 3 months, despite GFP protein expression decreasing during this time. GFP protein expression with hSyn increased more slowly, reaching a maximum at 3 months, which was equivalent to protein expression levels from CAG at that time point. Importantly, transgene expression driven by the hSyn promoter at 6 months was not silenced as previously reported, and GFP mRNA was continuing to rise even at the final 6-month time point. Thus, hSyn as a promoter for transgene expression demonstrates long-term durability but may require more time after vector administration to achieve steady-state levels. Because CAG had the highest GFP protein expression in our comparison, which was at 3 weeks post administration, the early kinetics of transgene expression from CAG was examined (1, 2, 5, and 10 days after injection). This analysis showed that GFP protein expression and GFP mRNA increased during the first 3 weeks after administration. Interestingly, vector DNA rapidly decreased 10-fold over the first 3 weeks following injection as it assembled into stable circular episomes and concatemers. Surprisingly, the processing of vector genomes into circular episomes and concatemers was continually dynamic up to 3 months after injection. These results provide novel insight into the dynamic processing of vector genomes and promoter-specific temporal patterns of transgene expression in the brain.
Actionable clinical decisions based on comprehensive genomic evaluation in asymptomatic adults (2015)

Whole-exome sequencing (WES) arises as a new approach in diagnosing individuals affected by multigenic and complex phenotypes. Herein, we aim to examine whether WES is useful in screening asymptomatic individuals for actionable interventions, which has not yet been established. Twenty-five healthy adults underwent WES, bioinformatics, and manual curation of their exomes. Six participants (24%) harbored significant, management-changing variants in cancer predisposition genes, American College of Medical Genetics, and genomics reportable cardiac diseases and pharmacogenomic biomarkers that have led to clinical recommendations and interventions. Furthermore, more than 80% of the participants (21) carried 1-3 genetic variants with an associated clinical guideline for an altered drug dosing or administration based on the FDA's table of pharmacogenomics. These results support WES potential not only to answer specific diagnostic questions presented by the relevant personal and/or family history but also to uncover clinically important genetic findings unrelated to the primary indication for sequencing.
Breast Cancer Growth Prevention by Statins (2006)

Statins are cholesterol-lowering drugs with pleiotropic activities including inhibition of isoprenylation reactions and reduction of signals driving cell proliferation and survival responses. The objectives of this study were to examine the effects of statins on breast cancer cells, both in vitro and in vivo, and to begin to determine their mechanism of action. We evaluated the effects of statins on breast cancer cell growth, phosphoprotein signaling intermediates, survival/apoptosis regulators, cell cycle regulators, and activated transcription factors. We also examined the in vivo effect of statin administration in a mouse ErbB2(+) breast cancer model. Only lipophilic statins had direct anticancer activity in vitro. Breast cancer cells with activated Ras or ErbB2 pathways seemed to be more sensitive than those overexpressing estrogen receptor, and this correlated with endogenous levels of activated nuclear factor kappaB (NF-kappaB). Key intermediates regulating cell survival by NF-kappaB activation, as well as cell proliferation by the mitogen activated protein kinase cascade, were among the earliest phosphoproteins influenced by statin treatment. These early effects were followed by declines in activator protein-1 and NF-kappaB activation and concordant changes in other mediators of proliferation and apoptosis. In vivo results showed that oral dosing of statins significantly inhibited the growth of a mouse mammary carcinoma. Lipophilic statins can exert direct anticancer activity in vitro by reducing proliferation and survival signals in susceptible breast cancer phenotypes. Tumor growth inhibition in vivo using a clinically relevant statin dose also seems to be associated with reduced tumor cell proliferation and survival. These findings provide supporting rationale for future statin trials in breast cancer patients.
ChemInform Abstract: Stibathiolanes: Synthesis, Solid‐State Structure, and Solution Behavior. (1991)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Editor's evaluation: Decoupled neoantigen cross-presentation by dendritic cells limits anti-tumor immunity against tumors with heterogeneous neoantigen expression (2023)

In vivo modeling of neoantigen-restricted heterogeneity shows that clonal expression of neoantigens enhances anti-tumor T cell responses by increasing the stimulatory capacity of dendritic cells in the lymph node.
Enhanced In-Plane Thermal Conductance of Thin Films Composed of Coaxially Combined Single-Walled Carbon Nanotubes and Boron Nitride Nanotubes (2020)

Carbon nanotubes (CNTs) and boron nitride nanotubes (BNNTs) are one-dimensional materials with high thermal conductivity and similar crystal structures. Additionally, BNNTs feature higher thermal stability in air than CNTs. In this work, a single-walled carbon nanotube (SWCNT) film was used as a template to synthesize a BNNT coating by the chemical vapor deposition (CVD) method to form a coaxial heterostructure. Then, a contact-free steady-state infrared (IR) method was adopted to measure the in-plane sheet thermal conductance of the as-synthesized film. The heterostructured SWCNT-BNNT film demonstrates an enhanced sheet thermal conductance compared with the bare SWCNT film. The increase in sheet thermal conductance shows a reverse relationship with SWCNT film transparency. An enhancement of over 80% (from ∼3.6 to ∼6.4 μW·K<sup>-1</sup>·sq<sup>-1</sup>) is attained when the BNNT coating is applied to an SWCNT film with a transparency of 87%. This increase is achieved by BNNTs serving as an additional thermal conducting path. The relationship between the thermal conductance increase and transparency of the SWCNT film is studied by a structured modeling of the SWCNT film. We also discuss the effect of annealing on the thermal conductance of SWCNTs before BNNT growth. Along with the preservation of high electrical conductance, the enhanced thermal conductance of the heterostructured SWCNT-BNNT films makes them a promising building block for thermal and optoelectronic applications.
Hepatitis B virus vaccine switch program for prevention ofde novohepatitis B virus infection in pediatric patients (2008)

The principal objective of this study was to evaluate the feasibility of Hepatitis B virus (HBV) vaccine switch program after 1-year Hepatitis B immunoglobulin (HBIG) for the prevention of de novo HBV (DNHBV) infection in pediatric recipients of hepatitis B core antibody (anti-HBc)-positive grafts. In this study, we enrolled pediatric recipients (n = 14), who had undergone living donor liver transplantation with anti-HBc-positive grafts between July 2000 and July 2005 and were followed up for over 24 months after transplantation. HBIG was given daily during the first week and intermittently in order to maintain anti-hepatitis B surface antigen (anti-HBs) titers greater than 200 IU/l until 12 months post-transplantation. Then the HBV vaccine was given intermittently as a substitute for HBIG when anti-HBs titer fell below 200 IU/l. The median follow-up duration after vaccination was 26.5 months, and a median of 2.03 doses of vaccine per year was required for the maintenance of anti-HBs titers greater than at least 100 IU/l. Two of the patients did not start the HBV vaccine due to sustained high anti-HBs titer. Eleven completed the HBV switch, whereas 1 was ongoing. With the HBV vaccine switch program, anti-HBs titers greater than 100 IU/l could be maintained conveniently and effectively.
Modification of the response of olfactory receptors to acetophenone by CYP1a2 (2017)

Olfaction is mediated by the binding of odorant molecules to olfactory receptors (ORs). There are numerous proteins in the nasal mucus, and they contribute to olfaction through various mechanisms. Cytochrome P450 (CYP) family members are known to be present in the olfactory epithelium and are thought to affect olfaction by enzymatic conversion of odorant molecules. In this study, we examined the effects of CYPs on the ligand responses of ORs in heterologous cells. Among the CYPs tested, co-expression of CYP1a2 significantly affected the responses of various ORs, including MOR161-2, to acetophenone. Conversion of acetophenone to methyl salicylate was observed in the medium of CYP1a2-expressing cells. MOR161-2-expressing cells exhibited significantly greater responses to methyl salicylate than to acetophenone. Finally, we analyzed the responses of olfactory neurons expressing MOR161-2 in vivo using the phosphorylated ribosomal protein S6 as a marker. MOR161-2 responded to both acetophenone and methyl salicylate in vivo. When the olfactory mucus was washed out by the injection of PBS to mouse nasal cavity, the response of MOR161-2 to acetophenone was reduced, while that to methyl salicylate did not change. Our data suggest that CYP1a2 affects OR activation by converting acetophenone to methyl salicylate.
Treating Pain Patients at Risk: Evaluation of a Screening Tool in Opioid-Treated Pain Patients With and Without Addiction (2003)

Patients receiving opioid treatment for chronic pain, many of whom were hospitalized with medical complications of substance abuse, were asked to complete a screening questionnaire to help validate a simple self-administered survey. Questions relating to tobacco abuse and prior treatment for drug and alcohol abuse distinguished patients with addiction and pain from opioid-treated chronic pain patients.
Design of the Language Replica for Hybrid PRAM-NUMA Many-core Architectures (2012)

Parallel programming is widely considered very demanding for an average programmer due to inherent asynchrony of underlying parallel architectures. In this paper we describe the main design principles and core features of Replica -- a parallel language aimed for high-level programming of a new paradigm of reconfigurable, scalable and powerful synchronous shared memory architectures that promise to make parallel programming radically easier with the help of strict memory consistency and deterministic synchronous execution of hardware threads and multi-operations.
Subharmonic destruction of generalized chaos synchronization (2001)

A bifurcation of transition that destroys generalized chaos synchronization is considered. This transition frequently occurs in regimes of subharmonic chaos entrainment where synchronization can be abruptly terminated due only to an almost unnoticeable change in the shape of the driving attractor. We explore the main cause of this sensitivity and ascertain the mechanism behind this transition.