gebhart/patrepeval huggingface dataset:
Syntheses and biological activities of parallel and antiparallel homo and hetero bis-cystine dimers of oxytocin and deamino-oxytocin. (1997)

New methods have been developed for the synthesis of disulfide-bridged homo and hetero peptide dimers (both parallel and antiparallel), as exemplified in the oxytocin and deamino-oxytocin families. The linear sequences were assembled by 9-fluorenyl-methyloxycarbonyl (Fmoc) solid-phase synthesis techniques, with orthogonal protection for the two beta-thiols by appropriate combinations of S-[(N'-methyl-N'-phenylcarbamoyl)sulfernyl] (Snm), S-acetamido-methyl (Acm) and S-2, 4, 6-trimethoxybenzyl (Tmob) groups. Two octapeptide-resins gave rise to four different nonapeptide amides, which were brought together in defined ways to provide access to four of the six possible dimeric products. For each dimer, the first disulfide bond was formed in solution by a directed method, and then the second disulfide bond was formed, without purification of the intermediates, by iodine oxidation. Final isolated yields of the desired pure dimers were in the 20% to 40% range. Biological activities ranged from 0.2% to 6% that of oxytocin, depending on the assay, and were in some cases considerably protracted. These data are consistent with the hypothesis that dimers revert slowly to monomers under the testing conditions.
P.145L: Late‐News Poster : Synthesis and Device Application of Carboline Derivatives as High Triplet Energy Materials for Blue Phosphorescent OLEDs (2013)

Abstract Three carboline derivatives, 9,9′‐m‐phenylenedi‐α‐carboline (NmCP1), 9,9′‐m‐phenylenedi‐β‐carboline (NmCP2), 9,9′‐m‐phenylendi‐γ‐carboline (NmCP3) were synthesized as high triplet energy host materials for blue phosphorescent organic light‐emitting diodes (PHOLEDs). Three carboline derivatives had nitrogen atom at different positions of carboline and the nitrogen atom position was correlated with the photophysical properties and device performances of carboline derivatives.
A high performance low magnetic field internal electrospray ionization-fourier transform ion cyclotron resonance mass spectrometer (1996)

A new in-magnetic field electrospray ionization (ESI) and Fourier transform ion cyclotron resonance mass spectrometer has been constructed and evaluated. This system is characterized by the use of multiple concentric cryopanels to achieve ultrahigh vacuum in the ion cyclotron resonance cell region, a probe-mounted internal ESI source, and a novel in-field shutter. Initial experiments demonstrate high resolution mass measurement capability at a field strength of 1 T. Mass resolution of 700,000 has been obtained for the 3+ charge state of Met-Lys-bradykinin (at m/z 440) generated by electrospray ionization. When electron impact ionization was employed, resolution in excess of 9,200,000 was achieved for nitrogen molecular ions (N 2 (+) ). Isotopic resolution for molecular ions of bovine ubiquitin (MW=8565 µ) also was achieved by using small ion populations.
Giant Fine Structure Splitting of the Bright Exciton in a Bulk MAPbBr3 Single Crystal (2019)

Exciton fine structure splitting in semiconductors reflects the underlying symmetry of the crystal and quantum confinement. Because the latter factor strongly enhances the exchange interaction, most work has focused on nanostructures. Here, we report on the first observation of the bright exciton fine structure splitting in a bulk semiconductor crystal, where the impact of quantum confinement can be specifically excluded, giving access to the intrinsic properties of the material. Detailed investigation of the exciton photoluminescence and reflection spectra of a bulk methylammonium lead tribromide single crystal reveals a zero magnetic field splitting as large as ∼200 μeV. This result provides an important starting point for the discussion of the origin of the large bright exciton fine structure splitting observed in perovskite nanocrystals.
Compound A, a Selective Glucocorticoid Receptor Modulator, Enhances Heat Shock Protein Hsp70 Gene Promoter Activation (2013)

Compound A possesses glucocorticoid receptor (GR)-dependent anti-inflammatory properties. Just like classical GR ligands, Compound A can repress NF-κB-mediated gene expression. However, the monomeric Compound A-activated GR is unable to trigger glucocorticoid response element-regulated gene expression. The heat shock response potently activates heat shock factor 1 (HSF1), upregulates Hsp70, a known GR chaperone, and also modulates various aspects of inflammation. We found that the selective GR modulator Compound A and heat shock trigger similar cellular effects in A549 lung epithelial cells. With regard to their anti-inflammatory mechanism, heat shock and Compound A are both able to reduce TNF-stimulated IκBα degradation and NF-κB p65 nuclear translocation. We established an interaction between Compound A-activated GR and Hsp70, but remarkably, although the presence of the Hsp70 chaperone as such appears pivotal for the Compound A-mediated inflammatory gene repression, subsequent novel Hsp70 protein synthesis is uncoupled from an observed CpdA-induced Hsp70 mRNA upregulation and hence obsolete in mediating CpdA's anti-inflammatory effect. The lack of a Compound A-induced increase in Hsp70 protein levels in A549 cells is not mediated by a rapid proteasomal degradation of Hsp70 or by a Compound A-induced general block on translation. Similar to heat shock, Compound A can upregulate transcription of Hsp70 genes in various cell lines and BALB/c mice. Interestingly, whereas Compound A-dependent Hsp70 promoter activation is GR-dependent but HSF1-independent, heat shock-induced Hsp70 expression alternatively occurs in a GR-independent and HSF1-dependent manner in A549 lung epithelial cells.
Computational examination of the electrophilic reaction on oxidative polymerization of phenyltrimethylsilane with sulfur chloride (1993)

Abstract Phenyltrimethylsilane possesses a higher HOMO energy (–9.34 eV) than nonsubstituted benzene (&gt;0.41 eV). The π electron of the phenyltrimethylsilane localizes on the benzene ring at the ipso position rather than at the para position. Two center energies calculated by the MNDO‐PM3 method indicate that the CSi bond is facilitated to cleave in comparison with the CH (para position) one of the benzene ring. Phenyltrimethylsilane and phenyl bis(trimethylsilane) were polymerized with sulfur chloride through the cationic oxidative polymerization. The product is isolated as oligo(p‐phenylene sulfide), with a melting point of 150–190°C. An electrophile attacks the carbon atom linked to the Si atom in phenyltrimethylsilane. The new synthetic route of PPS can be established on the basis of the computational calculation.
7. Two-Dose 4CMenB Vaccination in Adolescents Elicits a Bactericidal Activity against 15 Outbreak-Representative Meningococcal Strains (2020)

Abstract Background Meningococcal outbreaks have often been associated with N. meningitidis serogroup B (MenB) in high-income countries. We examined whether antibodies elicited by the 4-component MenB vaccine (4CMenB) in adolescents could induce complement-mediated bacterial killing of a panel of 14 genetically diverse MenB strains representative of outbreaks that occurred from 2001 to 2016 (11 from the US, 2 from the UK, and 1 from France). One N. meningitidis serogroup W (MenW) hyperendemic strain (UK, 2011) was also included in the analysis. Methods In a previous multicenter study (NCT02212457), adolescents aged 10-18y received 2 4CMenB doses 2 months apart. We tested individual sera collected from a subgroup of 20 US participants at pre-vaccination and 1 month post-second dose in a serum bactericidal assay with human complement (hSBA) against the meningococcal strain panel. Similarly, sera collected from 23 Chilean adolescents aged 11-17y (NCT00661713) were tested in a hSBA against a subset of 4 strains (3 from the US, 1 from the UK). Results At baseline, the percentage of US subjects with seroprotective titers (hSBA ≥ 1:4) ranged from 5% to 35%. One month after 4CMenB series completion, 65% to 100% had seroprotective titers (hSBA ≥ 1:4) against 11 out of the 14 MenB tested strains. The seroprotection rate was 45%, 25%, and 15% against the 3 remaining MenB strains. Against MenW, the percentage of adolescents with hSBA titers ≥ 1:4 was 15% at baseline and 95% one month after series completion. No significant changes in the percentage of subjects were observed when analysing hSBA titers ≥ 1:8. Moreover, the subset analysis indicated similar results for US and Chilean subjects for 3 out of 4 strains: the percentage of US vs Chilean subjects with hSBA titers ≥ 1:4 was 100% vs 100%; 80% vs 74%; 45% vs 52%. For the 4th strain, 65% of US subjects vs 91% of Chilean subjects showed a hSBA ≥ 1:4. Conclusion 4CMenB elicited bactericidal antibodies against a panel of 14 outbreak-representative MenB strains and 1 MenW hyperendemic strain in US adolescents. No major differences were detected in the bactericidal activity of Chilean subjects vaccinated with 4CMenB when tested against a subset of 4 MenB outbreak strains, suggesting that the immune response to 4CMenB is comparable in adolescents from different geographic areas. Disclosures Alessia Biolchi, n/a, GSK (Employee) Sara Tomei, n/a, GSK (Employee) Laura Santini, n/a, GSK (Employee) Rita La Gaetana, n/a, GSK Vaccines (Employee, Shareholder) Elena Mori, n/a, GSK (Employee) Patricia Novy, PhD, GSK (Employee, Shareholder) Rino Rappuoli, PhD, GSK (Employee) Rafik Bekkat-Berkani, M.D, GSK (Employee, Shareholder) Marzia Monica Giuliani, n/a, GSK (Employee, Shareholder) Mariagrazia Pizza, Biological Sciences, PhD, GSK Vaccines (Employee)
Equivalent qubit dynamics under classical and quantum noise (2007)

We study the dynamics of quantum systems under classical and quantum noise, focusing on decoherence in qubit systems. Classical noise is described by a random process leading to a stochastic temporal evolution of a closed quantum system, whereas quantum noise originates from the coupling of the microscopic quantum system to its macroscopic environment. We derive deterministic master equations describing the average evolution of the quantum system under classical continuous-time Markovian noise and two sets of master equations under quantum noise. Strikingly, these three equations of motion are shown to be equivalent in the case of classical random telegraph noise and proper quantum environments. Hence fully quantum-mechanical models within the Born approximation can be mapped to a quantum system under classical noise. Furthermore, we apply the derived equations together with pulse optimization techniques to achieve high-fidelity one-qubit operations under random telegraph noise, and hence fight decoherence in these systems of great practical interest.
The Vi Conjugate Typhoid Vaccine Is Safe, Elicits Protective Levels of IgG Anti-Vi, and Is Compatible with Routine Infant Vaccines (2011)

Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) of Salmonella enterica serovar Typhi (Vi) bound to recombinant exoprotein A of Pseudomonas aeruginosa (Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA or Haemophilus influenzae type b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of ≥ 3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of ≥ 3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA.
A Test Circuit for Extremely Low Gate Leakage Current Measurement of 10 aA for 80 000 MOSFETs in 80 s (2013)

We discuss the measurement accuracy of the test circuit, which can evaluate statistical characteristics of gate leakage current of small area metal-oxide-semiconductor field-effect transistors (MOSFETs) in a very short time. The accuracy and precision of the gate leakage current obtained by the test circuit are verified for a wide range. As a result it is confirmed that very accurate gate current of 10 <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">-17</sup> A ±10% is able to be measured with this method. Using this test circuit, we can evaluate the gate leakage current at a wide electric field range, which is important in discussing the conduction mechanism of gate leakage current.
In Vitro and In Vivo Studies of the Trypanocidal Effect of Novel Quinolines (2017)

Therapies for human African trypanosomiasis and Chagas disease, caused by <i>Trypanosoma brucei</i> and <i>Trypanosoma cruzi</i>, respectively, are limited, providing minimal therapeutic options for the millions of individuals living in very poor communities. Here the effects of 10 novel quinolines are evaluated <i>in silico</i> and by phenotypic studies using <i>in vitro</i> and <i>in vivo</i> models. Absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties revealed that most molecules did not infringe on Lipinski's rules, which is a prediction of good oral absorption. These quinolines showed high probabilities of Caco2 permeability and human intestinal absorption and low probabilities of mutagenicity and of hERG1 inhibition. <i>In vitro</i> screens against bloodstream forms of <i>T. cruzi</i> demonstrated that all quinolines were more active than the reference drug (benznidazole [Bz]), except for DB2171 and DB2192, with five (DB2187, DB2131, DB2186, DB2191, and DB2217) displaying 50% effective concentrations (EC<sub>50</sub>s) of <3 μM (4-fold lower than that of Bz). Nine quinolines were more effective than Bz (2.7 μM) against amastigotes, showing EC<sub>50</sub>s ranging from 0.6 to 0.1 μM. All quinolines were also highly active <i>in vitro</i> against African trypanosomes, showing EC<sub>50</sub>s of ≤0.25 μM. The most potent and highly selective candidates for each parasite species were tested in <i>in vivo</i> models. Results for DB2186 were promising in mice with <i>T. cruzi</i> and <i>T. brucei</i> infections, reaching a 70% reduction of the parasitemia load for <i>T. cruzi</i>, and it cured 2 out of 4 mice infected with <i>T. brucei</i> DB2217 was also active <i>in vivo</i> and cured all 4 mice (100% cure rate) with <i>T. brucei</i> infection.
Synthesis of new enantiomerically pure macrocycles containing phenanthroline subunits (2006)

New enantiomerically pure macrocycles have been prepared by combining 1,10-phenanthroline 2,9-dicarboxylic acid and two alpha-amino-acids linked through spacers. Different diamine linkers have been employed in order to modify the dimensions and the properties of the macrocycles whose structures have been studied by 1H and 13C NMR spectroscopy. The ability of the (L)-valine containing macrocycles to bind metal ions and phenolic molecules has been investigated by 1H NMR experiments and Molecular Mechanics calculations.
Detection of BRAF mutations in urine and plasma cell-free DNA: Application to the diagnosis and management of histiocytic disorder patients. (2014)

11012 Background: Histiocytosis patients (pts) have a high frequency of BRAFV600E mutations and respond to RAF inhibition but low tumor content and stromal contamination make detection in tissue biopsies challenging. Quantitative assessment of BRAFV600E mutations in tumor derived cell-free (cf) DNA may provide a convenient and reliable means of detecting this established biomarker and monitoring response to RAF targeted therapy. Here we compare the results of urine and plasma cfDNA BRAFV600E testing to tissue biopsy mutation testing in a large series of histiocytosis pts. Methods: Quantification of BRAFV600E was performed in cfDNA using droplet digital (dd) PCR (Trovagene, San Diego, CA). BRAFV600E analysis in tumor tissue was conducted using a variety of highly sensitive methodologies including locked nucleic acid and next-generation sequencing in CLIA-certified labs. Concordance between mutational analysis in tissue, plasma, and urine was determined. Results: 22 histiocytosis pts underwent cfDNA mutational analysis (18 Erdheim Chester Disease, 4 Langerhans Cell Histiocytosis). 20 pts also had CLIA-certified BRAFV600E mutational analysis in tissue (10 mutant, 6 wildtype, 4 test failure). All 10 BRAF-mutant pts based on tissue testing had a concordant positive cfDNA result in urine. Similarly, all 6 BRAF-wildtype pts based on tissue testing had a concordant negative cfDNA result in urine. 95% CI for concordance was 79-100%. Urine cfDNA was positive in 2 additional pts where tissue testing was unsuccessful. Plasma cfDNA testing did not identify BRAFV600E mutant pts who were not also positive by urine testing. Conclusions: Detection of actionable BRAF mutations by ddPCR in cfDNA is feasible and was completely concordant with CLIA-certified tumor mutation testing. Moreover, the ability to detect BRAF mutations in the urine of pts with repeated tumor tissue testing failure is potentially practice changing and demonstrates the clinical utility of cfDNA technologies. Mutations in cfDNA should be further investigated for longitudinal assessment of RAF-targeted therapy in pts with histiocytoses.
Trapped-Ion Quantum Computer with Robust Entangling Gates and Quantum Coherent Feedback (2022)

Quantum computers are expected to achieve a significant speed-up over classical computers in solving a range of computational problems. Chains of ions held in a linear Paul trap are a promising platform for constructing such quantum computers, due to their long coherence times and high quality of control. Here, we report on the construction of a small five-qubit universal quantum computer using 88 Sr + ions in a radiofrequency (rf) trap. All basic operations, including initialization, quantum logic operations, and readout, are performed with high fidelity. Selective two-qubit and single-qubit gates, implemented using a narrowline-width laser, comprise a universal gate set, allowing realization of any unitary on the quantum register. We review the main experimental tools and describe in detail unique aspects of the computer: the use of robust entangling gates and the development of a quantum coherent feedback system through electronmultiplying CCD camera acquisition. The latter is necessary for carrying out quantum error-correction protocols in future experiments.
Allograft nephrectomy versus nonallograft nephrectomy after failed renal transplantation: a systematic review by updated meta‐analysis (2021)

There is limited evidence regarding the impact of allograft nephrectomy (AN) on the long-term outcome of subsequent kidney re-transplantation compared with no prior allograft nephrectomy. The aim of the present study was to conduct a systematic review and meta-analysis to estimate the accumulation of evidence over time. Primary outcomes were 5-year graft and patient survival. Cochrane library, Google scholar, PubMed, Medline and Embase were systematically searched. Meta-analysis was conducted using both fixed- and random-effects models. Study quality was assessed in duplicate using the Newcastle-Ottawa scale. Sixteen studies were included, with a total of 2256 patients. All included studies were retrospective and comparative. There was no significant difference in 5-year graft survival (GS) [Hazard Ratio (HR) = 1.11, 95% Confidence Intervals (CI): 0.89, 1.38, P = 0.37, I<sup>2</sup> = 10%) or in 5-year patient survival (PS; HR = 0.70, 95% CI: 0.45, 1.10, P = 0.12, I<sup>2</sup> = 0%]. Patients in the AN cohort were significantly younger than patients in the nonallograft nephrectomy (NAN) cohort by one year. Prior allograft nephrectomy was associated with a significantly higher risk of delayed graft function (DGF), acute rejection, primary nonfunction (PNF), per cent of panel reactive antibodies (% PRA) and allograft loss of the subsequent transplant. Although, DGF, % PRA, acute rejection and primary nonfunction rates were significantly higher in the AN cohort, allograft nephrectomy prior to re-transplantation had no significant association with five-year graft and patient survival.
250-OR: Hypoproliferative CD8 Effector Memory (EM) Subsets Are Linked to Preservation of C-Peptide in Alefacept-Treated Recent-Onset Type 1 Diabetes (T1D) Subjects (2020)

In the ITN T1DAL trial, alefacept (LFA3-Ig fusion protein) preserved endogenous insulin production in 30% of recent onset T1D patients for two years after therapy. Although patients experienced immune alterations following treatment, including depletion of CD2hi effector T-cells and preservation of CD2lo regulatory T-cells, these effects were not predictive of overall response or outcome. However, using an unbiased approach and a combination of flow cytometry, RNA-sequencing, and CyTOF, we were able to identify a CD8 T-cell signature of response at ∼two years following treatment. Preservation of C-peptide was associated with a large transcriptional module (n= 738 genes; R= 0.4, p= 0.023) including activation and exhaustion-associated genes identified at two years following treatment using WGCNA. This module was further dissected into two distinct CD8 EM populations through correlation with hierarchically gated and clustered cytometry data. While both populations expressed multiple inhibitory receptors (IR) (TIGIT, KLRG1, T-bet, EOMES) and were hypo-responsive in in vitro proliferation assays, they were distinguished by higher expression either of markers seen in cytotoxic and terminally differentiated effector T cells (CD57+ Granzyme B+) or of PD-1. Gene expression signatures of both the CD57 and PD-1 subsets significantly overlapped with a previously identified partial exhaustion signature (p= 0.005, for both subsets). Our findings demonstrate an association of partially exhausted memory CD8 T-cells with beneficial clinical response to alefacept as we observed previously with teplizumab (anti-CD3) treatment. Our findings also demonstrate linkage of two phenotypically distinct IR-high, hypo-proliferative CD8 EM T-cell subsets with beneficial response. Together, our findings suggest that pathways regulating proliferation of EM CD8 cells may lead to successful immune interventions for T1D. Disclosure E. Serti: None. K.E. Diggins: None. V.S. Muir: None. T. Lu: None. E. Balmas: None. G.T. Nepom: None. S. Long: None. P. Linsley: Consultant; Self; Bristol-Myers Squibb. Funding National Institute of Diabetes and Digestive and Kidney Diseases/National Institute of Allergy and Infectious Diseases (UM1AI109565)