gebhart/patrepeval huggingface dataset:
A helicopter flight does not induce significant changes in systemic biomarker profiles (2009)

Whole-body vibration and noise are inherent characteristics of helicopter operations. The helicopter pilot is affected by vibration from both low-frequency noise and mechanical vibration sources. The way this energy is transmitted to different tissues and organs depends on intensity, frequency and resonance phenomena within the body. Whole-body vibration is known to affect the muscular and skeletal system in the lower part of the spine, but less is known about the response at the cellular level to this stimulation. In some studies, chronic pathological changes have been described in different types of tissue in people exposed to low-frequency noise and vibration. The aim of the present study was to investigate possible cellular reactions to acute exposure to low-frequency noise and vibration in a helicopter. Thirteen healthy males aged 38 (18-69) years were subjected to a 3.5 h helicopter flight in a Westland Sea King Rescue helicopter. Blood tests taken before and after the flight were analysed for more than 40 parameters, including acute phase reactants, markers of leucocyte and platelet activation, complement and hemostasis markers, as well as a broad panel of cytokines, chemokines, growth factors and cell adhesion molecules. The subjects served as their own controls. With the exception of an increase in vascular cell adhesion molecule-1 (VCAM-1) during the flight, no statistically significant changes in the biomarkers were found after controlling for diurnal variation in the control blood tests, which were observed independently of the helicopter flight. In conclusion, one helicopter flight does not induce measurable changes in systemic biomarkers.
Lead-Related Quantum Emitters in Diamond (2018)

We investigate the optical properties of quantum emitters formed in diamond after the implantation of Pb and subsequent high-temperature annealing. We find narrow-band emission in two spectral ranges, indicating multiple classes of Pb-related color centers.
Cancer among first-degree relatives of probands with invasive and borderline ovarian cancer*1 (1998)

These results suggest that relatives of patients with invasive and borderline ovarian cancer might share similar cancer risks and age-at-onset distributions.
Final report on EURAMET.QM-S8: Analysis of impurities in pure and balance gases used to prepare primary standard gas mixtures by the gravimetric method (2013)

This supplementary comparison (EURAMET.QM-S8) concerns the purity analysis of nitrogen as used in reference gas mixture preparation. This project was carried out without adding impurities to the gas used for this comparison, and is therefore more representative to evaluate the analysis of carbon monoxide, carbon dioxide, methane, oxygen, argon and water impurities in high-purity nitrogen. The analysis of the amount-of-substance fraction water was optional. Two 50 litre high purity nitrogen cylinders were purchased from a well-qualified supplier of specialty gases. The listed components were expected to be present in the pure nitrogen at the target levels as a result of the purification of the nitrogen. From the start of this comparison it was clear that the comparison may not lead to reference values for the constituents analysed. The results indicate that analyses of high purity gases are often limited by the limits of detection of analytical equipment used. The reports of the participating laboratories also indicate that there is no agreed method of determination of the uncertainty on a detection limit value. The results provide useful information on the performance of participants. For all analysed components there is reasonable agreement in results for LNE, VSL, METAS and NPL. For BAM only the argon result is in agreement. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by EURAMET, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).
ChemInform Abstract: Efficient Synthesis of Substituted Diarylsilanes. (2010)

Abstract No gaseous dichlorosilane is necessary for the preparation of the title compounds which proceeds without formation of by‐products.
GX15–070MS, a synthetic small molecule induces apoptosis in vitro and in vivo in chronic lymphocytic leukemia (2005)

3167 Chronic lymphocytic leukemia (CLL) B cells express high levels of anti-apoptotic proteins of the Bcl-2 family, such as Mcl-1, Bcl-XL, and Bcl-2. These proteins enhance the resistance of CLL cells to spontaneous and/or drug-induced apoptosis primarily by interacting with, and antagonizing the activity of mitochondria membrane pro-apoptotic proteins such as Bax and Bik. These interactions are governed by the binding to anti-apoptotic proteins via the BH3 domains of Bcl-2-family-member proteins. GX15–070MS is a small-molecule antagonist of the BH3-binding groove of the Bcl-2 family of proteins that can inhibit the interactions of Bcl-2 with proapoptotic molecules. We examined the activity of GX15–070MS on CLL cells in vitro and in vivo in a phase I/II clinical study initiated at our institution for patients with intermediate-risk or high-risk disease refractory to alkylating drugs, fludarabine-based regimens, and, in some cases also Alemtuzumab. Patients were treated with the initial escalating doses of 3.5 and 7 mg/m2. Administration of GX15–070 has been well tolerated and patients have not experienced any Grade 3 or Grade 4 toxicity. We have evaluated in vitro and in vivo the pro-apoptotic activity of GX15–070MS. GX15–070MS induced apoptosis in CLL-B cells in a time and dose-dependent manner with an IC50=10nM at 48 hours in culture. GX15–070MS induced apoptosis in CLL B cells independent of IgVH gene mutational status or ZAP-70 expression. In addition, we have analyzed the effect of this compound based on co-immunoprecipitations and Bcl-2/Mcl-1 mitochondrial displacement assays using video-confocal microscopy. These results indicate that GX15–070MS has activity inhibiting Bcl-2 family member proteins and inducing apoptosis in CLL B cells both in vitro and in vivo at dose ranges that are substantially below those estimated to induce toxicity in preclinical animal models. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Gemin X
Rapid route to efficient, scalable, and robust perovskite photovoltaics in air (2018)

RSPP is a unique up-scalable method to produce high quality photoactive perovskite in seconds in open-air.
Electrochemical characteristics of ultramicro-dimensioned SIROF electrodes for neural stimulation and recording (2019)

Ultra-small SIROF electrodes are capable of charge injection in buffered saline at levels above some reported thresholds for neural stimulation with microelectrodes.
Engineered Biosynthesis of Novel Polyketides:  Regiospecific Methylation of an Unnatural Substrate by the tcmO O-Methyltransferase (1996)

TcmO is an O-methyltransferase that methylates the C-8 hydroxyl to Tcm B3, a four-ring aromatic intermediate in the tetracenomycin biosynthetic pathway of Streptomyces glaucescens. The gene encoding this enzyme was expressed in Streptomyces coelicolor CH999 together with the actinorhodin polyketide synthase (PKS) gene cluster, which is responsible for the biosynthesis of 3,8-dihydroxy-methylanthraquinone carboxylic acid (DMAC) and its decarboxylated analog, aloesaponarin. The resulting recombinant strain produced approximately equal quantities of aloesaponarin and a new product but no DMAC. Spectroscopic analysis revealed that the novel polyketide was the 3-O-methylated analog of DMAC. An in vitro radioisotopic assay was developed for tcmO. The enzyme requires S-adenosylmethionine as a co-substrate. It has a Km of 3 microM and a kcat of 2.7 min-1 for DMAC. A series of monocyclic, bicyclic, and tricyclic aromatic compounds were also tested as candidate substrates in vitro. Remarkably, none was modified by tcmO within detectable limits of the assay. Together, these results highlight the interesting molecular recognition features of this enzyme. On one hand, there appears to be some flexibility in the number and structures of unreactive rings, since both Tcm and B3 and DMAC are good substrates. However, 6-methylsalicylic acid, a monocyclic analog of the reactive ring, is not recognized by the enzyme. Likewise, neither aloesaponarin (which only differs from DMAC in the reactive ring) nor carminic acid (which only differs in the distal nonreactive ring) is modified. Thus, the binding energy for the tcmO-catalyzed methyl transfer appears to involve significant contributions from both the aromaticity and the functionality of polycyclic substrates.
Dispersion of MOS capacitance-voltage characteristics resulting from the random channel dopant ion distribution (1994)

The random nature of the channel dopant ion distribution in silicon MOS devices is shown to cause a stretch-out of the capacitance-voltage characteristics. This nonideal behavior is caused by surface potential fluctuations which can be accurately modeled by assuming that the threshold voltage varies laterally over the area of the device with a normal distribution. The standard deviation of the threshold voltage distribution extracted from n- and p-channel MOS devices is presented for a wide range of substrate doping levels at both room and liquid-nitrogen temperature. The observed standard deviation of the threshold voltage is accurately predicted by a three-dimensional model based on the method of images which includes only the contribution from a random distribution of dopant ions in the depletion region. The contribution to the surface potential fluctuations from other sources is shown to be insignificant at high channel doping levels.< <ETX xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">&gt;</ETX>
First Synthesis of C8-Arylamine Adducts of 2′-Deoxyadenosine and Incorporation of the Phosphoramidite into an Oligonucleotide (2006)

The synthesis of C8-adducts of 2′-deoxyadenosine 7a,b with carcinogenic arylamines p-anisidine 4c and 4-aminobiphenyl 4b, their conversion into the phosphoramidites and successful incorporation into oligonucleotides are described.
High-resolution map of the Fc-functions mediated by COVID-19 neutralizing antibodies (2023)

ABSTRACT A growing body of evidence shows that Fc-dependent antibody effector functions play an important role in protection from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. To unravel the mechanisms that drive these responses, we analyzed the phagocytosis and complement deposition mediated by a panel of 482 human monoclonal antibodies (nAbs) neutralizing the original Wuhan virus, expressed as recombinant IgG1. Our study confirmed that nAbs no longer neutralizing SARS-CoV-2 Omicron variants can retain their Fc-functions. Surprisingly, we found that nAbs with the most potent Fc-function recognize the N- terminal domain, followed by those targeting Class 3 epitopes in the receptor binding domain. Interestingly, nAbs direct against the Class 1/2 epitopes in the receptor binding motif, which are the most potent in neutralizing the virus, were the weakest in Fc-functions. The divergent properties of the neutralizing and Fc- function mediating antibodies were confirmed by the use of different B cell germlines and by the observation that Fc-functions of polyclonal sera differ from the profile observed with nAbs, suggesting that not-neutralizing antibodies also contribute to Fc-functions. These data provide a high-resolution picture of the Fc-antibody response to SARS-CoV-2 and suggest that the Fc contribution should be considered for the design of improved vaccines, the selection of therapeutic antibodies and the evaluation of correlates of protection.
High-Throughput Synthesis of HepDirect Prodrugs of Nucleoside Monophosphates (2008)

A high-throughput phosphoramidite method for HepDirect prodrug synthesis was optimized on seven representative nucleosides, adenosine, inosine, guanosine, uridine, cytidine, AICA-riboside, and thymidine, each on a 5 mg scale. The variables optimized included (1) reaction time, (2) reaction temperature, (3) activating agent, (4) solvent, (5) purification method, and (6) stoichiometry. Preparative HPLC with mass-based fraction collection and yield determination from an ELSD standard curve enabled high-throughput. The optimized conditions for the representative nucleosides required 6 mol equiv of phosphoramidite to nucleoside and resulted in an average HPLC determined yield of 31 +/- 14% and HPLC purity of 93 +/- 3%.
Supplementary Figure 3 from Combination Immunotherapy after ASCT for Multiple Myeloma Using MAGE-A3/Poly-ICLC Immunizations Followed by Adoptive Transfer of Vaccine-Primed and Costimulated Autologous T Cells (2023)

&lt;p&gt;PDF file - 40KB, ELISA Antibody Responses for the PCV (Prevnar-13(registered trademark)).&lt;/p&gt;
Time‐of‐flight secondary ion mass spectrometry of wet and dry chemically treated display glass surfaces (2017)

Abstract Display glasses meet the demands of the flat panel display industry vis‐à‐vis their composition, flatness, and forming processes. Here, we report the high‐resolution time‐of‐flight secondary ion mass spectrometry (ToF‐SIMS) characterization of Corning ® EAGLE XG ® , a widely used display glass, and subsequent chemometric analyses of these data. Samples analyzed included the as‐formed glass, fracture surfaces from remelt bars, and as‐formed surfaces subsequently exposed to process‐relevant treatments, including strong acids and bases, two industrial detergents, and an atmospheric‐pressure plasma treatment. Elemental signals in the positive ion ToF‐SIMS spectra respond to surface treatments. Acidic conditions leach non‐silica components from the surfaces, while basic treatments extract these species less efficiently. The detergents leave residues of Na + and K + . The atmospheric pressure (AP) plasma treatment had little effect on the surface composition, while the melt surface differs significantly from the bulk fracture surface. Above ca. 75 m/z, the negative ion spectra are dominated by two series of homologous cluster ions with compositions of Si n O 2 n +2 Al − and Si m HO 2 m +1 H − . The presence of these clusters suggests that analogous structures exist at the near surface regions of the samples. In a series of multivariate curve resolution (MCR) analyses, two or three MCR components captured &gt;95% of the variance in the data for these samples.
Increase in the proliferative capacity of human myoblasts by using the T antigen under the vimentin promoter control (1997)

Normal myoblasts have a strictly limited growth potential and senesce after a defined number of population doubling. The objective of this study was to determine whether the proliferative capacity of human myoblasts could be extended without inhibiting myogenic differentiation. We have established a stable transfected human myoblast cell line that expresses the SV 40 large T antigen under the control of the human vimentin promoter. We show that these cells have an increased proliferative capacity compared with that of normal myoblasts. Indeed, the final proliferative capacity was increased to 19 passages (5 for normal myoblasts). Moreover, they retained their capacity to differentiate fully, as indicated by their morphology and electrophysiological properties as well as by the expression of different markers of differentiation. The generation of human myogenic cell lines with the ability to proliferate for a longer period of time than primary myoblasts and while retaining the capacity to differentiate into myotubes could provide a valuable tool for the derivation of cell lines from human diseased muscle cells.
Hessian-free low-mode conformational search for large-scale protein loop optimization: application to c-jun N-terminal kinase JNK3 (2000)

A Hessian-free low-mode search algorithm has been developed for large-scale conformational searching. The new method is termed LLMOD, and it utilizes the ARPACK package to compute low-mode eigenvectors of a Hessian matrix that is only referenced implicitly, through its product with a series of vectors. The Hessian × vector product is calculated utilizing a finite difference formula based on gradients. LLMOD is the first conformational search method that can be applied to fully flexible, unconstrained protein structures for complex loop optimization problems. LLMOD has been tested on a particularly difficult model system, c-jun N-terminal kinase JNK3. We demonstrate that LLMOD was able to correct a P38/ERK2/HCL-based homology model that grossly misplaced the crucial glycine-rich loop in the ATP-binding site. © 2000 John Wiley & Sons, Inc. J Comput Chem 22: 21–30, 2001
K-252a and staurosporine selectively block autophosphorylation of neurotrophin receptors and neurotrophin-mediated responses. (1992)

The same receptor tyrosine kinase (RTK) can mediate strikingly different biological responses in a fibroblast as opposed to a neuron. We have compared the rapidly induced tyrosine phosphorylations mediated by various RTKs in both NIH3T3 fibroblasts and in the PC12 neuronal precursor cell line and found that each RTK induces a distinct pattern of protein tyrosine phosphorylations in the two cell types. These findings are consistent with a model in which various cell types present a given RTK with different menus of signal transduction components, allowing the same RTK to elicit fundamentally distinct biological responses. Although there are obvious overlaps in the tyrosine phosphorylations induced by different RTKs in the same cell, there are also clear differences. The attempt to dissect these differences revealed that the kinase inhibitors K-252a and staurosporine inhibit RTK autophosphorylation and thus the biological consequences of receptor/ligand interaction. These inhibitors displayed substantially greater specificity for a subset of RTKs (including the neurotrophin receptors) than for other RTKs and acted as remarkably selective blockers of neurotrophin action in both neuronal and nonneuronal cells. A potential therapeutic application for these inhibitors is discussed.
PtrR (YneJ) is a novel E. coli transcription factor regulating the putrescine stress response and glutamate utilization (2020)

ABSTRACT Although polyamines, such as putrescine (Ptr), induce envelope stress for bacteria, they are important as nitrogen and carbon sources. Ptr utilization in Escherichia coli involves protein glutamylation, and glutamate stands at a crossroads between catabolism and anabolism. This communication reports that the transcription factor YneJ, here renamed PtrR, is involved in the regulation of a small regulatory RNA gene, fnrS , and an operon, yneIHGF , encoding succinate-semialdehyde dehydrogenase, Sad (YneI), glutaminase, GlsB (YneH), and several other genes. The yneI promoter is activated during putrescine utilization under nitrogen/carbon starvation conditions, and we show that PtrR is important for the putrescine stress response. It is also a repressor of fnrS gene expression, involved in the cascade regulation of mRNA synthesis for the marA and sodB genes, involved in antibiotic responses. PtrR transcriptional regulation of fnrS leads to a regulatory cascade induced by this small RNA that affects mRNA levels of ompF and the multidrug resistance regulator, MarA. We propose that PtrR functions as a dual activator/repressor, and that its regulation is important for the responses to different stress conditions involving L-glutamine/L-glutamate and putrescine utilization. IMPORTANCE Putrescine is an important source of nitrogen for many organisms, but it also induces stress. Although its metabolism has been studied extensively, the regulatory mechanisms that control the stress response are still poorly understood. This study reveals that the HTH-type transcriptional regulator, YneJ in Escherichia coli , here re-named PtrR, is important for the putrescine stress response, in part because it plays a role in outer membrane porin regulation as a sensor in a regulatory cascade. Direct PtrR transcriptional regulation of the fnrS, yneI (sad), gltS and ptrR genes is documented and rationalized, and nine PtrR binding sites were identified using ChIP-Exo. A ptrR mutant exhibited altered resistance to a tetracycline group of antibiotics under microaerophilic conditions, suggesting that PtrR indirectly controls expression of porin genes such as ompF .
Genetically engineered T-cell therapy for HPV-associated epithelial cancers: A first in human, phase I/II clinical trial. (2018)

3019 Background: Engineered T-cell therapy is an emerging treatment for hematological cancers. In epithelial cancers, its study has been limited. Human papillomavirus (HPV)-16+ epithelial cancers constitutively express the HPV E6 oncoprotein. We investigated treatment of metastatic HPV-16+ cancers with T cells that target E6 by an engineered T-cell receptor (E6 T cells). Methods: A phase I/II, single-center, clinical trial was conducted. Eligible subjects had a metastatic HPV-16+ cancer from any primary tumor site and had received prior platinum-based therapy. Treatment consisted of a one-time, intravenous infusion of E6 T cells. A lymphocyte-depleting conditioning regimen and systemic aldesleukin were also administered. Results: Twelve subjects were treated on this protocol. Dose-limiting toxicity was not encountered (maximum dose was 1.7 x 1011 T cells). Transduction efficiency range was 45-76%. Infused E6 T cells demonstrated engraftment at one month post-treatment in all patients (range 4-53%). Two of nine subjects in the highest dose cohort experienced tumor responses. A subject with a 6-month partial response had complete regression of one lesion and partial regression of two lesions, which were subsequently resected; the subject has no evidence of disease three years after treatment. Resected tumor from this subject demonstrated infiltration by E6 T cells that showed increased expression of the inhibitory molecule PD-1 as compared to E6 T cells in the peripheral blood (26% vs 2%). Genomic analyses were performed on the tumors of two subjects who did not respond to treatment. One subject displayed a frameshift deletion in the interferon-gamma response gene, IFNGR1. Another demonstrated loss of heterozygosity (LOH) in chromosome 6 with deletion of HLA-A*02:01, the necessary restriction element for this therapy. A subject who responded to treatment did not demonstrate genomic alterations in these pathways. Conclusions: Engineered T cells targeting E6 can induce regression of HPV+ epithelial cancers. Treatment resistance may be related to T-cell inhibition by PD-1, tumor evasion by antigen processing and presentation loss, and defects in interferon-response pathways. Clinical trial information: NCT02280811.
Evaluation of Angiogenic Inhibitors with an in vivo Quantitative Angiogenesis Method Using Agarose Microencapsulation and Mouse Hemoglobin Enzyme‐linked Immunosorbent Assay (1996)

In the present work, using a previously reported in vivo quantitative tumor-angiogenesis model, we attempted to ascertain whether this animal model is suitable for practical use in monitoring inhibitors of tumor angiogenesis. Mouse sarcoma-180 cells, human A431 cells or rat C6 cells microencapsulated in agarose beads were implanted s.c. into C57BL/6 mice. The level of blood vessel induction at the agarose pellet site was evaluated using mouse hemoglobin enzyme-linked immunosorbent assay on day 10 after implantation. Hydrocortisone, tetrahydro-S, medroxyprogesterone acetate, pentosan polysulfate and suramin inhibited blood vessel growth in our in vivo tumor-angiogenesis assay system, and heparin enhanced the antiangiogenic effects of hydrocortisone and tetrahydro-S. These results are almost entirely consistent with those observed in common assay systems, and suggest that this method may be useful for the identification and quantitative evaluation of inhibitors of tumor angiogenesis.