gebhart/patrepeval huggingface dataset:
Combined Analysis of Antigen Presentation and T-cell Recognition Reveals Restricted Immune Responses in Melanoma (2018)

The quest for tumor-associated antigens (TAA) and neoantigens is a major focus of cancer immunotherapy. Here, we combine a neoantigen prediction pipeline and human leukocyte antigen (HLA) peptidomics to identify TAAs and neoantigens in 16 tumors derived from seven patients with melanoma and characterize their interactions with their tumor-infiltrating lymphocytes (TIL). Our investigation of the antigenic and T-cell landscapes encompassing the TAA and neoantigen signatures, their immune reactivity, and their corresponding T-cell identities provides the first comprehensive analysis of cancer cell T-cell cosignatures, allowing us to discover remarkable antigenic and TIL similarities between metastases from the same patient. Furthermore, we reveal that two neoantigen-specific clonotypes killed 90% of autologous melanoma cells, both <i>in vitro</i> and <i>in vivo</i>, showing that a limited set of neoantigen-specific T cells may play a central role in melanoma tumor rejection. Our findings indicate that combining HLA peptidomics with neoantigen predictions allows robust identification of targetable neoantigens, which could successfully guide personalized cancer immunotherapies.<b>Significance:</b> As neoantigen targeting is becoming more established as a powerful therapeutic approach, investigating these molecules has taken center stage. Here, we show that a limited set of neoantigen-specific T cells mediates tumor rejection, suggesting that identifying just a few antigens and their corresponding T-cell clones could guide personalized immunotherapy. <i>Cancer Discov; 8(11); 1366-75. ©2018 AACR.</i> <i>This article is highlighted in the In This Issue feature, p. 1333</i>.
Structure and organization of plasmid genes required to produce the translation inhibitor microcin C7 (1995)

The translation inhibitor microcin C7 (MccC7) is a linear heptapeptide whose N terminus has been replaced by an N-formyl group and whose C terminus has been replaced by the phosphodiester of 5'-adenylic acid and n-aminopropanol (J. I. Guijarro, J. E. González-Pastor, F. Baleux, J. L. San Millán, M. A. Castilla, M. Rico, F. Moreno, and M. Delepierre, J. Biol. Chem. 270:23520-23532, 1995). MccC7 production and immunity determinants lie on a 6.2-kb region of the Escherichia coli plasmid pMccC7. This region was entirely sequenced. It contains six open reading frames, which were shown to be true genes by different complementary approaches. Five genes, mccABCDE, which are transcribed in the same direction, are required to produce mature extracellular microcin. The sixth gene, mccF, adjacent to mccE, is transcribed in the opposite direction and encodes specific self-immunity. Genes mccA to -E constitute an operon transcribed from a promoter (mccp) located upstream of mccA. mccA is 21 nucleotides long and encodes the unmodified heptapeptide (J. E. González-Pastor, J. L. San Millán, and F. Moreno, Nature [London] 369:281, 1994). A comparison of predicted gene polypeptide products with those included in databases shows that an 81-amino-acid stretch of MccB is strikingly homologous to fragments of the same length of proteins ThiF and ChlN from E. coli, HesA from Anabaena sp. strain PCC7120, and UBA1, the ubiquitin-activating enzyme from different eukaryotic species. MccC displays several hydrophobic domains, suggesting a transmembrane location. The carboxyl end of MccE displays 41.2% identity with RimL, a protein required to acetylate the ribosome protein L12 from E. coli. In the absence of the other mcc genes, mccA impairs the growth of host cells, suggesting that unmodified MccA has antibiotic activity. A model for MccC7 biosynthesis, export, and immunity is proposed.
ATP as a mediator of erythrocyte‐dependent regulation of skeletal muscle blood flow and oxygen delivery in humans (2012)

In healthy human beings, blood flow to dynamically contracting skeletal muscle is regulated primarily to match oxygen (O(2)) delivery closely with utilisation. This occurs across a wide range of exercise intensities, as well as when exercise is combined with conditions that modify blood O(2) content. The red blood cells (RBCs), the primary O(2) carriers in the blood, contribute to the regulation of the local processes matching O(2) supply and demand. This is made possible by the ability of RBCs to release the vasoactive substance adenosine triphosphate (ATP) in response to reductions in erythrocyte and plasma O(2), as well as to other adjuvant metabolic and mechanical stimuli. The regulatory role of RBCs in human beings is supported by the observations that, i) exercising skeletal muscle blood flow responds primarily to changes in the amount of O(2) bound to the erythrocyte haemoglobin molecules, rather than the amount of O(2) in plasma, and ii) exercising muscle blood flow can almost double (from 260 to 460 ml min(-1) 100 g(-1)) with alterations in blood O(2) content, such that O(2) delivery and are kept constant. Besides falling blood O(2) content, RBCs release ATP when exposed to increased temperature, reduced pH, hypercapnia, elevated shear stress and augmented mechanical deformation, i.e. conditions that exist in the microcirculation of active skeletal muscle. ATP is an attractive mediator signal for skeletal muscle blood flow regulation, not only because it can act as a potent vasodilator, but also because of its sympatholytic properties in the human limb circulations. These properties are essential to counteract the vasoconstrictor effects of concurrent increases in muscle sympathetic nerve activity and circulating vasoconstrictor substances during exercise. Comparison of the relative vasoactive potencies and sympatholytic properties of ATP, other nucleotides, and adenosine in human limbs, suggests that intravascular ATP exerts its vasodilator and sympatholytic effects directly, and not via its degradation compounds. In conclusion, current evidence clearly indicates that RBCs are involved directly in the regulation of O(2) supply to human skeletal muscle during dynamic exercise. Further, intravascular ATP might be an important mediator in local metabolic sensing and signal transduction between the RBCs and the endothelial and smooth muscle cells in the vascular beds of skeletal muscle.
Evidence for coiled-coil dimer formation by an Epstein-Barr virus transactivator that lacks a heptad repeat of leucine residues. (1990)

Two regions of the Epstein-Barr virus (EBV) BZLF1 gene product, ZEBRA, share sequence homology with c-Fos, one of which corresponds to the DNA binding domain of c-Fos. ZEBRA does not, however, contain the heptad repeat of leucines present in the dimerization domains of leucine zipper proteins. Here it is shown that ZEBRA binds its recognition sites as a homodimer and that the region adjacent to the basic DNA binding domain is essential for dimerization. This region contains a 4-3 repeat of predominantly hydrophobic residues, which is precisely in register with the hydrophobic heptad repeat present in the leucine zipper proteins with respect to the basic DNA binding domain. A mutational analysis of ZEBRA supports a model for dimerization involving a coiled-coil interaction. These results indicate that a heptad repeat of leucines is not a structural requirement for formation of coiled-coil dimers by transcription factors.
Lipid Alterations and Decline in the Incidence of Coronary Heart Disease in the Helsinki Heart Study (1988)

In the Helsinki Heart Study, a randomized five-year, double-blind trial, a 34% reduction in the incidence of coronary heart disease (CHD) was observed in dyslipidemic men treated with gemfibrozil. Averaged over the five years of the trial, gemfibrozil therapy produced, compared with placebo, mean decreases of 10% in serum total cholesterol level, 14% in non-high-density lipoprotein (HDL) cholesterol level, 11% in low-density lipoprotein (LDL) cholesterol level, 35% in triglyceride level, and a mean increase of 11% in HDL cholesterol level from baseline levels measured prior to treatment. While changes in HDL cholesterol level were similar in all Fredrickson types, the effect on concentrations of total cholesterol and LDL cholesterol was largest in type IIA and on LDL minimal in type IV. The reduction of CHD incidence over placebo was largest in type IIB and smallest in type IIA. The lipid changes were dependent on lipid levels prior to treatment and on compliance with the medication regimen. When risk factors for CHD, including age, blood pressure, smoking and drinking habits, baseline lipid levels, and exercise and relative weight, were controlled by applying the Cox proportional hazards model, the changes in serum HDL and LDL cholesterol levels were both statistically significantly associated with the decline in CHD incidence within the gemfibrozil-treated group. The large decrease in serum triglyceride levels had relatively small effect on CHD incidence. Thus, the results of this study, together with earlier observations, suggest that both elevating HDL and lowering LDL cholesterol levels are effective in the primary prevention of CHD.
In Pursuit of Zero: Polymer Brushes that Resist the Adsorption of Proteins (2009)

Abstract Protein resistant or “non‐fouling” surfaces are of great interest for a variety of biomedical and biotechnology applications. This article briefly reviews the development of protein resistant surfaces, followed by recent research on a new methodology to fabricate non‐fouling surfaces by surface‐initiated polymerization. We show that polymer brushes synthesized by surface‐initiated polymerization that present short oligo(ethylene glycol) side chains are exceptionally resistant to protein adsorption and cell adhesion. The importance of the protein and cell resistance conferred by these polymer brushes is illustrated by their use as substrates for the fabrication of antibody microarrays that exhibit femtomolar limits of detection in complex fluids such as serum and blood with relaxed requirements for intermediate wash steps. This example highlights the important point that the reduction in background noise afforded by protein‐resistant surfaces can greatly simplify the development of ultrasensitive heterogeneous, surface‐based clinical and proteomic assays with increased sensitivity and utility.
Electronic beam induced poling of BaTiO3 thin films (1993)

The effect of electron beam irradiation on second harmonic generation of BaTiO3 thin films was studied. Enhanced second harmonic intensity was measured from BaTiO3 thin films irradiated by electron beams of 10, 15, and 25 keV using a scanning electron microscope. The enhancement of the second harmonic generations is attributed to the electron beam-induced poling of the film. The effectiveness of the electron beam irradiation on second harmonic generation enhancement is comparable to that of the corona poling of the film at room temperature. This electron beam induced poling technique offers a promising method for nonlinear optical device fabrication.
Suppression of threshold voltage variation in MTCMOS/SIMOX circuit operating below 0.5 V (2002)

We describe a power-switch transistor for a multi-threshold CMOS/SIMOX circuit operating at extremely low supply voltage below 0.5 V. Power-switch transistors with a gate-body-connected variable-threshold MOSFET and a conventional MOSFET were fabricated and measured. The variable-threshold MOSFET suppressed the variation in threshold voltage and improved current drivability. Suppression of variation in gate delay time and improvement in the delay time were demonstrated at low supply voltage below 0.5 V.
Reprogramming of proline and glutamine metabolism contributes to the proliferative and metabolic responses regulated by oncogenic transcription factor c-MYC (2012)

In addition to glycolysis, the oncogenic transcription factor c-MYC (MYC) stimulates glutamine catabolism to fuel growth and proliferation of cancer cells through up-regulating glutaminase (GLS). Glutamine is converted to glutamate by GLS, entering the tricarboxylic acid cycle as an important energy source. Less well-recognized, glutamate can also be converted to proline through Δ(1)-pyrroline-5-carboxylate (P5C) and vice versa. This study suggests that some MYC-induced cellular effects are due to MYC regulation of proline metabolism. Proline oxidase, also known as proline dehydrogenase (POX/PRODH), the first enzyme in proline catabolism, is a mitochondrial tumor suppressor that inhibits proliferation and induces apoptosis. MiR-23b* mediates POX/PRODH down-regulation in human kidney tumors. MiR-23b* is processed from the same transcript as miR-23b; the latter inhibits the translation of GLS. Using MYC-inducible human Burkitt lymphoma model P493 and PC3 human prostate cancer cells, we showed that MYC suppressed POX/PRODH expression primarily through up-regulating miR-23b*. The growth inhibition in the absence of MYC was partially reversed by POX/PRODH knockdown, indicating the importance of suppression of POX/PRODH in MYC-mediated cellular effects. Interestingly, MYC not only inhibited POX/PRODH, but also markedly increased the enzymes of proline biosynthesis from glutamine, including P5C synthase and P5C reductase 1. MYC-induced proline biosynthesis from glutamine was directly confirmed using (13)C,(15)N-glutamine as a tracer. The metabolic link between glutamine and proline afforded by MYC emphasizes the complexity of tumor metabolism. Further studies of the relationship between glutamine and proline metabolism should provide a deeper understanding of tumor metabolism while enabling the development of novel therapeutic strategies.
The genome-wide dynamics of the binding of Ldb1 complexes during erythroid differentiation (2010)

One of the complexes formed by the hematopoietic transcription factor Gata1 is a complex with the Ldb1 (LIM domain-binding protein 1) and Tal1 proteins. It is known to be important for the development and differentiation of the erythroid cell lineage and is thought to be implicated in long-range interactions. Here, the dynamics of the composition of the complex-in particular, the binding of the negative regulators Eto2 and Mtgr1-are studied, in the context of their genome-wide targets. This shows that the complex acts almost exclusively as an activator, binding a very specific combination of sequences, with a positioning relative to transcription start site, depending on the type of the core promoter. The activation is accompanied by a net decrease in the relative binding of Eto2 and Mtgr1. A Chromosome Conformation Capture sequencing (3C-seq) assay also shows that the binding of the Ldb1 complex marks genomic interaction sites in vivo. This establishes the Ldb1 complex as a positive regulator of the final steps of erythroid differentiation that acts through the shedding of negative regulators and the active interaction between regulatory sequences.
A Mycobacterium ESX-1–Secreted Virulence Factor with Unique Requirements for Export (2007)

Specialized secretion systems of pathogenic bacteria commonly transport multiple effectors that act in concert to control and exploit the host cell as a replication-permissive niche. Both the Mycobacterium marinum and the Mycobacterium tuberculosis genomes contain an extended region of difference 1 (extRD1) locus that encodes one such pathway, the early secretory antigenic target 6 (ESAT-6) system 1 (ESX-1) secretion apparatus. ESX-1 is required for virulence and for secretion of the proteins ESAT-6, culture filtrate protein 10 (CFP-10), and EspA. Here, we show that both Rv3881c and its M. marinum homolog, Mh3881c, are secreted proteins, and disruption of RD1 in either organism blocks secretion. We have renamed the Rv3881c/Mh3881c gene espB for ESX-1 substrate protein B. Secretion of M. marinum EspB (EspBM) requires both the Mh3879c and Mh3871 genes within RD1, while CFP-10 secretion is not affected by disruption of Mh3879c. In contrast, disruption of Mh3866 or Mh3867 within the extRD1 locus prevents CFP-10 secretion without effect on EspBM. Mutants that fail to secrete only EspBM or only CFP-10 are less attenuated in macrophages than mutants failing to secrete both substrates. EspBM physically interacts with Mh3879c; the M. tuberculosis homolog, EspBT, physically interacts with Rv3879c; and mutants of EspBM that fail to bind Mh3879c fail to be secreted. We also found interaction between Rv3879c and Rv3871, a component of the ESX-1 machine, suggesting a mechanism for the secretion of EspB. The results establish EspB as a substrate of ESX-1 that is required for virulence and growth in macrophages and suggests that the contribution of ESX-1 to virulence may arise from the secretion of multiple independent substrates.
Detection of small bunches of ions using image charges (2018)

A concept for detection of charged particles in a single fly-by, e.g. within an ion optical system for deterministic implantation, is presented. It is based on recording the image charge signal of ions moving through a detector, comprising a set of cylindrical electrodes. This work describes theoretical and practical aspects of image charge detection (ICD) and detector design and its application in the context of real time ion detection. It is shown how false positive detections are excluded reliably, although the signal-to-noise ratio is far too low for time-domain analysis. This is achieved by applying a signal threshold detection scheme in the frequency domain, which - complemented by the development of specialised low-noise preamplifier electronics - will be the key to developing single ion image charge detection for deterministic implantation.
Regulatory Variation Within and Between Species (2011)

Understanding how individuals differ from one another and from closely related species is a fundamental problem in biology. Recent evidence suggests that much of the variation both within and between species is due to differential gene regulation. Here we review differential gene regulation focusing on evolutionary-developmental (evo-devo) biology, global comparison of genomic sequences, whole-genome gene expression, and transcription factor (TF) binding profiles. We also explore the relationship between divergence rate of regulatory sequences, coding sequences, and TF binding events using several different measures and discuss their implications in the context of evolution of regulatory networks. Finally, we discuss the current status and future challenges in relating regulatory variation to the divergence across and within species.
Effect of viscosity and interfacial tension on particle size of cellulose acetate trimellitate microspheres (1991)

The influence of the viscosity of the internal and external phases and the interfacial tension between the two phases, in the emulsion type of microencapsulation system was investigated. The viscosity of mineral oil (external phase) was measured by a capillary viscometer and the viscosity of cellulose acetate trimellitate solution (internal phase) was measured by a Brookfield viscometer. The viscosity of the two phases were measured prior to mixing and at 5 and 60 min after mixing the phases. It was observed that the viscosity of the mineral oil phase prior to mixing had little effect on the average diameter of the microspheres, until a high concentration of light mineral oil was used. A graph of viscosity ratio of the internal phase to the external phase shows that a minimum viscosity ratio may be required before particle size increases. Results are discussed with respect to viscosity effects of mineral oil and polymer solution, as influenced by the solvent uptake by the mineral oil. The interfacial tension between the two phases was measured by pendant drop method. Interfacial tension was measured at 5 and 60 min after the two phases came in contact. The interfacial tension between the mineral oil and polymer solution ranged up to 7 dyne/cm and the particle size was not affected appreciably by the interfacial tension. Particle size and morphological analysis of the microspheres were determined using microscopy and scanning electron microscope.
Tumor microenvironmental genomic alterations in juvenile nasopharyngeal angiofibroma (2011)

A similar pattern of gene expression and chromosomal imbalances in both exponents would suggest a common mechanism of functional regulation. AURKB, FGF18, and SUPT16H were identified as potential molecular markers in JNA.
Splitting of the interband absorption edge in Au (1975)

Very accurate ellipsometric measurements were made on very pure bulk samples of Au at room temperature in the 1.0-3.5-eV energy region. A model calculation has been developed for $d$ bands to Fermi-surface transitions occuring near the $X$ point in the Brillouin zone and it is shown that for topological reasons the line shape of the imaginary part of the dielectric constant ${\ensuremath{\epsilon}}_{2}$ is considerably different from what has been calculated for $L$ transitions. Using this model to fit our experimental data it has been possible to show that the absorption edge in Au is "split" into two separate contributions. The onset of $X$ transitions has been located at 1.94 eV while the onset of the $L$ transitions has been confirmed at 2.45 eV in excellent agreement with previous determinations.
A Cationic Iridium Complex Bearing an Imidazol-2-ylidene Ligand as Alkene Hydrogenation Catalyst (2001)

The new cationic iridium carbene complex [Ir(cod)(py)(SIMes)]PF6 (2) has been synthesized by reaction of [Ir(cod)(py)2]PF6 with SIMes. Complex 2 is an active hydrogenation catalyst capable of hydrogenating simple olefins at room temperature and atmospheric pressure of hydrogen.
Amino Acids of the Bacterial Toxin SopE Involved in G Nucleotide Exchange on Cdc42 (2003)

RhoGTPases are central switches in all eukaryotic cells. There are at least two known families of guanine nucleotide exchange factors that can activate RhoGTPases: the Dbl-like eukaryotic G nucleotide exchange factors and the SopE-like toxins of pathogenic bacteria, which are injected into host cells to manipulate signaling. Both families have strikingly different sequences, structures, and catalytic core elements. This suggests that they have emerged by convergent evolution. Nevertheless, both families of G nucleotide exchange factors also share some similarities: (a) both rearrange the G nucleotide binding site of RhoGTPases into virtually identical conformations, and (b) two SopE residues (Gln-109SopE and Asp-124SopE) engage Cdc42 in a similar way as equivalent residues of Dbl-like G nucleotide exchange factors (i.e. Asn-810Dbs and Glu-639Dbs). The functional importance of these observations has remained unclear. Here, we have analyzed the effect of amino acid substitutions at selected SopE residues implicated in catalysis (Asp-124SopE, Gln-109SopE, Asp-103SopE, Lys-198SopE, and Gly-168SopE) on in vitro catalysis of G nucleotide release from Cdc42 and on in vivo activity. Substitutions at Asp-124SopE, Gln-109SopE, and Gly-168SopE severely reduced the SopE activity. Slight defects were observed with Asp-103SopE variants, whereas Lys-198SopE was not found to be required in vitro or in vivo. Our results demonstrate that G nucleotide exchange by SopE involves both catalytic elements unique to the SopE family (i.e. 166GAGA169 loop, Asp-103SopE) and amino acid contacts resembling those of key residues of Dbl-like guanine nucleotide exchange factors. Therefore, besides all of the differences, the catalytic mechanisms of the SopE and the Dbl families share some key functional aspects.
A wireless biomedical instrument for evidence-based tissue wound characterization (2010)

Patients' skin integrity has long been an issue of concern in nursing homes and hospitals. Overall incidence of pressure ulcers for hospitalized patients is as high as 50%. The estimated cost of treating pressure ulcers ranges from $5,000 to $40,000 for each ulcer, depending on severity. A smart compact capacitive sensing wireless handheld system is presented which measures Sub-Epidermal Moisture (SEM) as a mean to detect and monitor early symptoms of ulcer development. The system was successfully verified in trials with 30 volunteers and is currently deployed for clinical trials in four nursing homes.