gebhart/patrepeval huggingface dataset:
Data from Feasibility and Safety of Personalized, Multi-Target, Adoptive Cell Therapy (IMA101): First-in-Human Clinical Trial in Patients with Advanced Metastatic Cancer (2023)

&lt;div&gt;Abstract&lt;p&gt;IMA101 is an actively personalized, multi-targeted adoptive cell therapy (ACT), whereby autologous T cells are directed against multiple novel defined peptide-HLA (pHLA) cancer targets. HLA-A*02:01-positive patients with relapsed/refractory solid tumors expressing ≥1 of 8 predefined targets underwent leukapheresis. Endogenous T cells specific for up to 4 targets were primed and expanded &lt;i&gt;in vitro&lt;/i&gt;. Patients received lymphodepletion (fludarabine, cyclophosphamide), followed by T-cell infusion and low-dose IL2 (Cohort 1). Patients in Cohort 2 received atezolizumab for up to 1 year (NCT02876510). Overall, 214 patients were screened, 15 received lymphodepletion (13 women, 2 men; median age, 44 years), and 14 were treated with T-cell products. IMA101 treatment was feasible and well tolerated. The most common adverse events were cytokine release syndrome (Grade 1, &lt;i&gt;n&lt;/i&gt; = 6; Grade 2, &lt;i&gt;n&lt;/i&gt; = 4) and expected cytopenias. No patient died during the first 100 days after T-cell therapy. No neurotoxicity was observed. No objective responses were noted. Prolonged disease stabilization was noted in three patients lasting for 13.7, 12.9, and 7.3 months. High frequencies of target-specific T cells (up to 78.7% of CD8&lt;sup&gt;+&lt;/sup&gt; cells) were detected in the blood of treated patients, persisted for &gt;1 year, and were detectable in posttreatment tumor tissue. Individual T-cell receptors (TCR) contained in T-cell products exhibited broad variation in TCR avidity, with the majority being low avidity. High-avidity TCRs were identified in some patients’ products. This study demonstrates the feasibility and tolerability of an actively personalized ACT directed to multiple defined pHLA cancer targets. Results warrant further evaluation of multi-target ACT approaches using potent high-avidity TCRs.&lt;/p&gt;&lt;p&gt;&lt;i&gt;&lt;a href="https://aacrjournals.org/cancerimmunolres/article/doi/10.1158/2326-6066.CIR-23-0160" target="_blank"&gt;See related Spotlight by Uslu and June, p. 865&lt;/a&gt;&lt;/i&gt;&lt;/p&gt;&lt;/div&gt;
Surface roughness effects on the solar reflectance of cool asphalt shingles (2008)

We analyze the solar reflectance of asphalt roofing shingles that are covered with pigmented mineral roofing granules. The reflecting surface is rough, with a total area approximately twice the nominal area. We introduce a simple analytical model that relates the 'micro-reflectance' of a small surface region to the 'macro-reflectance' of the shingle. This model uses a mean field approximation to account for multiple scattering effects. The model is then used to compute the reflectance of shingles with a mixture of different colored granules, when the reflectances of the corresponding mono-color shingles are known. Simple linear averaging works well, with small corrections to linear averaging derived for highly reflective materials. Reflective base granules and reflective surface coatings aid achievement of high solar reflectance. Other factors that influence the solar reflectance are the size distribution of the granules, coverage of the asphalt substrate, and orientation of the granules as affected by rollers during fabrication.
Vaccines Against Respiratory Syncytial Virus and Parainfluenza Viruses (2016)

The genomes of RSV (Fig. 1B) and the PIVs (PIV3 is shown in Fig. 1C) are approximately 15.5 kb in length and are organized into gene units that are separated by short intergenic sequences (IG, bold in Fig. 1C). Gene start (GS) sequences and gene end (GE) sequences direct initiation and termination of mRNA transcription for each gene unit. Transcription occurs in a sequential manner in which the viral polymerase scans the genome from the 30 end and transcribes each gene unit in turn. Polymerase drop-off between gene units leads to a transcriptional gradient in which gene units closer to the 30 end of the genome are transcribed more efficiently than downstream genes.
[PP.07.17] VITAMIN D RECEPTOR GENE POLYMORPHISMS, FGF-23 AND FETUIN-A IN ESSENTIAL HYPERTENSION (2016)

Objective: The association between FokI and BsmI vitamin D receptor gene (VDR) polymorphisms and cardiovascular risk was analyzed with contrasting results. Low plasmatic concentrations of fetuin-A, a negative regulator of vascular calcification, and high levels of fibroblast growth factor 23 (FGF-23), a calcium and phosphate metabolism regulator, seem to be associated with higher cardiovascular mortality. Our aim was to evaluate possible association between FokI and BsmI VDR polymorphisms and plasma concentrations of fetuin-A and FGF-23 in essential hypertension. Design and method: Seventy-one patients with essential hypertension underwent clinical blood pressure evaluation, 24-hour ambulatory blood pressure monitoring, assays of 25-hydroxyvitamin D (25[OH]D), FGF-23 and fetuin-A serum levels, and FokI and BsmI VDR polymorphisms analysis. Results: No significant correlations were found either between 25[OH]D and FGF-23, or between 25[OH]D and fetuin-A. When patients were divided according to FokI and BsmI genotypes, we did not observe any significant difference in 25[OH]D, fetuin-A and FGF23 values among different subgroups. Considering FGF-23 median value (79 pg/ml), we did not find any association between a genotype or allele and FGF-23 serum level higher than cut-off. A similar result was obtained by evaluating the association between FokI and BsmI genotypes or alleles, and fetuin-A levels lower than median value (1,2 g/L). Conclusions: In essential hypertension FokI and BsmI VDR polymorphisms does not seem to be associated either with high FGF-23 serum levels, or with low fetuin-A plasma concentrations.
All-optical chromatic dispersion monitoring of a 40-Gb/s RZ signal by measuring the XPM-generated optical tone power in a highly nonlinear fiber (2006)

We experimentally demonstrate an all-optical chromatic dispersion (CD) monitoring technique potential for ultrahigh-speed systems. A monochromatic continuous wave probe is coupled with the tapped-off data signal into a highly nonlinear fiber. An optical tone that is sensitive to CD is generated near the probe wavelength due to the cross-phase modulation effect and is used for CD monitoring. The monitoring window is /spl plusmn/42 ps/nm for 40-Gb/s return-to-zero systems. This monitoring technique is simple and needs no modification at the transmitter.
Pump-Probe Spectroscopy of Exciton Dynamics in (6,5) Carbon Nanotubes (2007)

We investigate exciton dynamics in isopycnically enriched (6,5) nanotube-DNA suspensions using femtosecond time-resolved pump−probe spectroscopy. The ground state recovery is characterized by a t-0.45 ± 0.03 power law behavior, indicative of a one-dimensional diffusion-limited reaction that is tentatively attributed to subdiffusive trapping of dark excitons. Spectral transients of bright singlet excitons within the E11 and E22 manifolds exhibit a photobleach (PB) and a photoabsorption (PA) signal of similar strength. The PA is blue-shifted with respect to the PB-signal by 7.5 meV and is attributed to a transition from the dark singlet exciton to a + state within the two exciton E11 manifold.
Novel Tracking Power Supply for Linear Power Amplifiers (2008)

Conventional linear power amplifiers (LPAs) show a high output voltage quality but are characterized by high power losses and/or low power density. Therefore, there is a growing interest in increasing the efficiency of LPAs, e.g., for the realization of high power testing voltage sources. In this paper, a high-frequency isolated boost-type tracking power supply (TPS) system is proposed for the conditioning of the input voltage of an LPA. The output voltage of the TPS is varied according to the voltage to be formed by the LPA so that the voltage drop across the power amplifier output transistors is reduced to low values. This results in a significant increase of the total system efficiency. The operating principle of the proposed system is described. A design method for the output filter using the power supply rejection ratio of the LPA is proposed. This method ensures that the amplifier output voltage has minimal switching frequency components. Furthermore, a control system design method is presented that ensures good performance in the control of the constant inductor current of the switch-mode tracking stage. Finally, the theoretical considerations are verified by measurements on a 1-kW laboratory prototype.
Establishment of Embryonic Stem Cells and Generation of Genetically Modified Rats (2011)

Authentic embryonic stem (ES) cells are derived from the inner cell mass (ICM) of preimplantation blastocysts in rodents. ES cells have been routinely derived since 1981 (Evans & Kaufman, 1981; Martin, 1981). They are capable of generating germline chimeras following injection into blastocysts. A very large number of knockin/knockout mice have been produced so far, leading to significant progress in both basic research and clinical investigation. However, recent reports indicate that the phenotypes of knockout mice sometimes do not correspond to human diseases (Rogers et al., 2008). Thus, the ES cells of other species, especially rats, have been desired for the generation of new animal models for human diseases. In 2008, we successfully established rat ES cells with a chimeric contribution (Ueda et al., 2008). Soon after our report, authentic rat ES cells that could complete a germline transmission were established (Buehr et al., 2008; Li et al., 2008). These reports suggest that a removal of serum from a culture medium is necessary for maintaining the pluripotency of rat ES cells (Kawamata & Ochiya, 2010a). However, despite the assertion in these reports, we recently established high-quality rat ES cells by using a combination of 20% serum and signaling inhibitors. Furthermore, this culture condition enabled the ES cells to receive gene manipulation, leading to obtaining genetically modified rats via germline transmission. We also discovered an indispensable technique during a blastocyst injection process for the generation of germline chimeras (Kawamata & Ochiya, 2010b). This new technology should provide valuable animal models for the study of human diseases by the induction of gene-targeting manipulations in the rat ES cells. In this chapter, we discuss the techniques for the establishment of rat ES cells compared to mouse ES cells and the creation of genetically modified rats.
Inhibition of NF-κB by S-Nitrosylation (2001)

It is not clear if redox regulation of transcription is the consequence of direct redox-related modifications of transcription factors, or if it occurs at some other redox-sensitive step. One obstacle has been the inability to demonstrate redox-related modifications of transcription factors in vivo. The redox-sensitive transcriptional activator NF-kappaB (p50-p65) is a case in point. Its activity in vitro can be inhibited by S-nitrosylation of a critical thiol in the DNA-interacting p50 subunit, but modulation of NF-kappaB activity by nitric oxide synthase (NOS) has been attributed to other mechanisms. Herein we show that cellular NF-kappaB activity is in fact regulated by S-nitrosylation. We observed that both S-nitrosocysteine and cytokine-activated NOS2 inhibited NF-kappaB in human respiratory cells or murine macrophages. This inhibition was reversed by addition of the denitrosylating agent dithiothreitol to cellular extracts, whereas NO bioactivity did not affect the TNFalpha-induced degradation of IkappaBalpha or the nuclear translocation of p65. Recapitulation of these conditions in vitro resulted in S-nitrosylation of recombinant p50, thereby inhibiting its binding to DNA, and this effect was reversed by dithiothreitol. Further, an increase in S-nitrosylated p50 was detected in cells, and the level was modulated by TNFalpha. Taken together, these data suggest that S-nitrosylation of p50 is a physiological mechanism of NF-kappaB regulation.
Serpin B9 controls tumor cell killing by CAR T cells (2023)

Overall, the data indicate that serpin B9 is a resistance mediator for CAR T cell-mediated tumor cell killing that should be inhibited or bypassed to improve CAR T-cell responses.
Improving upon Nature: Active Site Remodeling Produces Highly Efficient Aldolase Activity toward Hydrophobic Electrophilic Substrates (2012)

The substrate specificity of enzymes is frequently narrow and constrained by multiple interactions, limiting the use of natural enzymes in biocatalytic applications. Aldolases have important synthetic applications, but the usefulness of these enzymes is hampered by their narrow reactivity profile with unnatural substrates. To explore the determinants of substrate selectivity and alter the specificity of Escherichia coli 2-keto-3-deoxy-6-phosphogluconate (KDPG) aldolase, we employed structure-based mutagenesis coupled with library screening of mutant enzymes localized to the bacterial periplasm. We identified two active site mutations (T161S and S184L) that work additively to enhance the substrate specificity of this aldolase to include catalysis of retro-aldol cleavage of (4S)-2-keto-4-hydroxy-4-(2'-pyridyl)butyrate (S-KHPB). These mutations improve the value of k(cat)/K(M)(S-KHPB) by >450-fold, resulting in a catalytic efficiency that is comparable to that of the wild-type enzyme with the natural substrate while retaining high stereoselectivity. Moreover, the value of k(cat)(S-KHPB) for this mutant enzyme, a parameter critical for biocatalytic applications, is 3-fold higher than the maximal value achieved by the natural aldolase with any substrate. This mutant also possesses high catalytic efficiency for the retro-aldol cleavage of the natural substrate, KDPG, and a >50-fold improved activity for cleavage of 2-keto-4-hydroxy-octonoate, a nonfunctionalized hydrophobic analogue. These data suggest a substrate binding mode that illuminates the origin of facial selectivity in aldol addition reactions catalyzed by KDPG and 2-keto-3-deoxy-6-phosphogalactonate aldolases. Furthermore, targeting mutations to the active site provides a marked improvement in substrate selectivity, demonstrating that structure-guided active site mutagenesis combined with selection techniques can efficiently identify proteins with characteristics that compare favorably to those of naturally occurring enzymes.
[Neer's shoulder prosthesis: results according to etiology]. (1994)

The outcome of 80 glenohumeral arthroplasties with the Neer prosthesis in 77 patients with degenerative or inflammatory shoulder disease was evaluated after a mean follow-up of three years five months. The arthroplasties were performed because of intractable pain and functional disability due to destruction of the glenohumeral joint. The postoperative rehabilitation program focused on full recovery of joint motion and function in 65 cases and on joint stability with partial recovery of joint motion and function in 15 cases. According to the criteria developed by Neer, the outcome was excellent or satisfactory in 75% of cases and unsatisfactory in 25%. Constant's scores adjusted for age and gender varied widely across diagnostic categories, from a high of 76% in centered glenohumeral osteoarthritis (n = 40) to lows of 59% in rheumatoid arthritis (n = 21) and 45% in posttraumatic osteoarthritis (n = 10) or eccentric osteoarthritis due to cuff disruption (n = 9). At reevaluation, 70% of patients had little or no pain and 90% were satisfied with the outcome. The mean increase in flexion of the arm (39 degrees) was markedly influenced by the diagnosis. The increases in lateral rotation (mean 35 degrees) and medial rotation (four vertebral levels) of the arm were especially appreciated by the patients as having a very beneficial effect on the ability to perform everyday tasks. Complications included instability in three cases (two anterior dislocations and one posterior dislocation), glenoid component loosening in 11 cases (of which only four required reoperation) and rotator cuff tear in eight cases. Our results add to the existing evidence that nonconstrained shoulder implants, such as the Neer prosthesis, are both safe and effective in alleviating pain and improving joint function. They should be used in patients with refractory pain, disability due to restrictions in external and medial rotation of the arm and roentgenographic evidence of glenohumeral joint space loss.
Inactivation of Corynebacterium glutamicum NCgl0452 and the Role of MgtA in the Biosynthesis of a Novel Mannosylated Glycolipid Involved in Lipomannan Biosynthesis (2006)

Mycobacterium tuberculosis PimB has been demonstrated to catalyze the addition of a mannose residue from GDP-mannose to a monoacylated phosphatidyl-myo-inositol mannoside (Ac(1)PIM(1)) to generate Ac(1)PIM(2). Herein, we describe the disruption of its probable orthologue Cg-pimB and the chemical analysis of glycolipids and lipoglycans isolated from wild type Corynebacterium glutamicum and the C. glutamicum::pimB mutant. Following a careful analysis, two related glycolipids, Gl-A and Gl-X, were found in the parent strain, but Gl-X was absent from the mutant. The biosynthesis of Gl-X was restored in the mutant by complementation with either Cg-pimB or Mt-pimB. Subsequent chemical analyses established Gl-X as 1,2-di-O-C(16)/C(18:1)-(alpha-d-mannopyranosyl)-(1-->4)-(alpha-d-glucopyranosyluronic acid)-(1-->3)-glycerol (ManGlcAGroAc(2)) and Gl-A as the precursor, GlcAGroAc(2). In addition, C. glutamicum::pimB was still able to produce Ac(1)PIM(2), suggesting that Cg-PimB catalyzes the synthesis of ManGlcAGroAc(2) from GlcAGroAc(2). Isolation of lipoglycans from C. glutamicum led to the identification of two related lipoglycans. The larger lipoglycan possessed a lipoarabinomannan-like structure, whereas the smaller lipoglycan was similar to lipomannan (LM). The absence of ManGlcA-GroAc(2) in C. glutamicum::pimB led to a severe reduction in LM. These results suggested that ManGlcAGroAc(2) was further extended to an LM-like molecule. Complementation of C. glutamicum::pimB with Cg-pimB and Mt-pimB led to the restoration of LM biosynthesis. As a result, Cg-PimB, which we have assigned as MgtA, is now clearly defined as a GDP-mannose-dependent alpha-mannosyltransferase from our in vitro analyses and is involved in the biosynthesis of ManGlcAGroAc(2).
Genome Sequence of Shigella flexneri Serotype 5a Strain M90T Sm (2012)

Bacteria of the genus Shigella are a major cause of death worldwide (L. von Seidlein et al., PLoS Med. 3:e353, 2006). We sequenced the genome of Shigella flexneri strain M90T Sm (serotype 5a) and compared it to the published genome sequence of S. flexneri strain 8401 (serotype 5b).
3D‐Structured Photodetectors Based on 2D Transition‐Metal Dichalcogenide (2021)

3D‐structured transition‐metal dichalcogenides (TMDCs) are attracting significant attention in the field of photodetection owing to their remarkable and superior electronic and optoelectronic properties. This review outlines the optical properties of graphene and TMDCs. The recent progress in 2D‐planar graphene and TMDC‐based photodetectors are discussed. In addition, the recent advances in the different types of 3D‐structured TMDCs and their heterostructures used in photodetectors are elaborated in detail. These 3D‐structured TMDC‐based photodetectors exhibit enhanced optoelectronic properties compared to 2D‐planar photodetectors. Finally, this review concludes with the latest developments in 3D‐structured graphene and TMDC‐based photodetectors, and discusses the present challenges and future prospects for high‐performance photodetectors.
Self-recovering transceivers for block transmissions: filterbank precoders and decision-feedback equalizers (2003)

Transmitter induced redundancy using FIR filterbanks can be used to equalize FIR channels irrespective of channel zeros and facilitate blind channel estimation. At the receiver end, linear or non-linear (DFE) FIR filterbanks can be applied to recover the transmitted data. Closed form expressions are derived for the FIR linear or DFE filterbank receivers. By applying blind channel estimation methods, the resulting DFE-framework becomes self-recovering. Extensive simulations illustrate the merits of our designs.
Figure S3 from The Transcriptional Regulator Sin3A Contributes to the Oncogenic Potential of STAT3 (2023)

&lt;p&gt;Data show the effects of resveratrol on TSGs expression and ALK+ cell survival&lt;/p&gt;
Supplementary Table 7 from Genome-Wide CpG Island Profiling of Intraductal Papillary Mucinous Neoplasms of the Pancreas (2023)

&lt;p&gt;PDF file - 70K&lt;/p&gt;
Ion Channel Pharmacology Under Flow: Automation Via Well-Plate Microfluidics (2012)

Automated patch clamping addresses the need for high-throughput screening of chemical entities that alter ion channel function. As a result, there is considerable utility in the pharmaceutical screening arena for novel platforms that can produce relevant data both rapidly and consistently. Here we present results that were obtained with an innovative microfluidic automated patch clamp system utilizing a well-plate that eliminates the necessity of internal robotic liquid handling. Continuous recording from cell ensembles, rapid solution switching, and a bench-top footprint enable a number of assay formats previously inaccessible to automated systems. An electro-pneumatic interface was employed to drive the laminar flow of solutions in a microfluidic network that delivered cells in suspension to ensemble recording sites. Whole-cell voltage clamp was applied to linear arrays of 20 cells in parallel utilizing a 64-channel voltage clamp amplifier. A number of unique assays requiring sequential compound applications separated by a second or less, such as rapid determination of the agonist EC(50) for a ligand-gated ion channel or the kinetics of desensitization recovery, are enabled by the system. In addition, the system was validated via electrophysiological characterizations of both voltage-gated and ligand-gated ion channel targets: hK(V)2.1 and human Ether-à-go-go-related gene potassium channels, hNa(V)1.7 and 1.8 sodium channels, and (α1) hGABA(A) and (α1) human nicotinic acetylcholine receptor receptors. Our results show that the voltage dependence, kinetics, and interactions of these channels with pharmacological agents were matched to reference data. The results from these IonFlux™ experiments demonstrate that the system provides high-throughput automated electrophysiology with enhanced reliability and consistency, in a user-friendly format.
Exploring 3D navigation (2001)

We present a task-based taxonomy of navigation techniques for 3D virtual environments, used to categorize existing techniques, drive exploration of the design space, and inspire new techniques. We briefly discuss several new techniques, and describe in detail one new techniques, Speed-coupled Flying with Orbiting. This technique couples control of movement speed to camera height and tilt, allowing users to seamlessly transition between local environment-views and global overviews. Users can also orbit specific objects for inspection. Results from two competitive user studies suggest users performed better with Speed-coupled Flying with Orbiting over alternatives, with performance also enhanced by a large display.
Converting Stöber Silica and Mediterranean Sand to High Surface Area Silicon by a Reaction under Autogenic Pressure at Elevated Temperatures (2009)

We report on a reaction to convert Stöber silica or Mediterranean sand to high surface area silicon (HSAS). The starting silica and/or the sand are reduced by magnesium under the autogenic pressure of the reactants at 750 °C for 5 h. After the MgO is removed, HSAS is formed. The surface areas are 200 and 86 m2/g for the product obtained from the Stöber silica and sand, respectively. The morphology of the final product is almost identical to that of the precursor silica. The products are stable in air because a thin layer of SiO2 is present on the surface of the silicon. We have detected luminescence from the HSAS in the wavelength region of 626−640 nm.