gebhart/patrepeval huggingface dataset:
N-terminal proteoforms may engage in different protein complexes (2023)

Abstract Alternative translation initiation and alternative splicing may give rise to N-terminal proteoforms, proteins that differ at their N-terminus compared to their canonical counterparts. Such proteoforms can have altered localizations, stabilities and functions. While proteoforms generated from splice variants can be engaged in different protein complexes, it remained to be studied to what extent this applies to N-terminal proteoforms. To address this, we mapped the interactomes of several pairs of N-terminal proteoforms and their canonical counterparts. First, we generated a catalogue of N-terminal proteoforms found in the HEK293T cellular cytosol from which 22 pairs were selected for interactome profiling. Additionally, we provide evidence for the expression of several N-terminal proteoforms, identified in our catalogue, across different human tissues as well as tissue-specific expression, highlighting their biological relevance. Protein-protein interaction profiling revealed that the overlap of the interactomes for both proteoforms is generally high, showing their functional relation. We also showed that N-terminal proteoforms can be engaged in new interactions and/or lose several interactions compared to their canonical counterpart, thus further expanding the functional diversity of proteomes.
Association of maintenance of pre-existing memory T-cell responses following anti-CTLA-4 antibody treatment with improved overall survival. (2014)

3016 Background: While treatment with anti-CTLA-4 antibody can induce clinical responses in advanced cancer patients, the immunobiology and biomarkers associated with improved clinical outcomes is unknown. Methods: We used a next-generation sequencing to track changes in the T cell repertoire in 46 patients with metastatic castration resistant prostate cancer (CRPC) or metastatic melanoma (MM). Peripheral blood mononuclear cells were obtained from patients prior to and during treatment with anti-CTLA-4 antibody. mRNA was amplified with locus-specific primer sets for T cell receptor (TCR) beta, and the amplified products were sequenced. Sequence reads were used to quantitate absolute TCR frequencies using standardized clonotype determination algorithms with normalization by spiked reference TCR sequences. Following clonotype quantitation, the kinetics of specific T cell clonotypes were tracked with anti-CTLA-4 treatment. Naïveand memory T cells were also sorted and sequenced to define changes in these subsets. Results: CTLA-4 blockade resulted in both expansion and loss of T cell clonotypes, consistent with a global turnover of the T cell repertoire. While this treatment increased TCR diversity as reflected in the number of unique TCR clonotypes, the vast majority of change occurred in the memory T cell pool. Whereas the number of clonotypes that increased with treatment was not associated with clinical outcome, declines of the highest frequency clonotypes following treatment were associated with short overall survival. These declines were not evident in patients with longer overall survival. This association was seen in both CRPC (p<0.05) and MM patients (P<0.01, two-sided Mann Whitney). Conclusions: Together, these results indicate that CTLA-4 blockade induces T-cell repertoire evolution and diversification. However, improved clinical outcomes are associated with maintenance of pre-existing high frequency memory T cells during treatment. These clones may represent the presence of pre-existing T cells that may be relevant in the anti-tumor response. Detection of these high frequency T cell clones could help to identify patients that benefit from treatment.
Fabrication of Monolithic Bridge Structures by Vacuum‐Assisted Capillary‐Force Lithography (2009)

Bridging the gap: Vacuum-assisted capillary force lithography (CFL) allows the fabrication of monolithic, suspended bridge structures (see picture) by exploiting partial curing kinetics and vacuum-assisted hydraulic filling. A small portion of the base microstructure (<4 µm) is molded to create a bridge structure by simply applying a nanoscale mold with the impression of channels, meshes, or circles.
Taxol-induced growth arrest and apoptosis is associated with the upregulation of the Cdk inhibitor, p21WAF1/CIP1, in human breast cancer cells (2012)

The anticancer agent, taxol, stabilizes tubulin polymerization, resulting in arrest at the G2/M phase of the cell cycle and apoptotic cell death. However, the molecular mechanism of this growth inhibition and apoptosis is poorly understood. In this study, we used MCF-7 and MDA-MB-231 human breast carcinoma cells which have different estrogen receptor (ER) and tumor suppressor p53 statuses to examine the mechanisms of taxol-induced growth inhibition and apoptosis. Treatment of the cells with taxol resulted in a time-dependent inhibition of cell viability, which was accompanied by an accumulation of cells at G2/M and the sub-G1 apoptotic region, determined by flow cytometric analysis. Furthermore, chromatin condensation, DNA ladder formation and proteolytic cleavage of poly(ADP-ribose) polymerase (PARP) in both cell lines were observed following treatment with taxol, indicating the occurrence of apoptotic cell death. Western blot analysis using whole cell lysates from MCF-7 and MDA-MB-231 cells treated with taxol demonstrated that taxol treatment inhibited expression of cyclin A and cyclin B1 proteins in a time-dependent manner. The inhibitory effects of taxol on cell growth and apoptosis induced by taxol were also associated with the downregulation of Wee1 kinase expression and a marked induction in the activity of the cyclin-dependent kinase inhibitor, p21WAF/CIP1. Furthermore, taxol elevated p21 promoter activity in both cell lines. These findings suggest that taxol-induced G2/M arrest and apoptosis in human breast carcinoma cells is mediated through the ER- and p53-independent upregulation of p21.
PHA-680632, a Novel Aurora Kinase Inhibitor with Potent Antitumoral Activity (2006)

PHA-680632 is the first representative of a new class of Aurora inhibitors with a high potential for further development as an anticancer therapeutic. On treatment, different cell lines respond differentially, suggesting the absence of critical cell cycle checkpoints that could be the basis for a favorable therapeutic window.
Continuous‐flow liquid microjunction surface sampling probe connected on‐line with high‐performance liquid chromatography/mass spectrometry for spatially resolved analysis of small molecules and proteins (2013)

Spatially resolved sampling, separation, and detection of small molecules and proteins from surfaces can be accomplished using a continuous-flow liquid microjunction surface sampling probe coupled on-line with HPLC/MS detection.
In vivo evaluation of bioresorbable polylactide implants for cervical graft containment in an ovine spinal fusion model (2004)

The bioresorbable polymer cervical graft containment system appears to provide a safe and effective alternative for cervical fusion, and warrants further clinical evaluation for its use in single-level anterior cervical discectomy and fusion without postoperative orthosis.
A 90nm low-power FPGA for battery-powered applications (2006)

Programmable logic devices such as FPGAs are useful for a wide range of applications. However, FPGAs are not commonly used in battery-powered applications because they consume more power than ASICs and lack power management features. In this paper, we describe the design and implementation of Pika, a low-power FPGA core targeting battery-powered applications such as those in consumer and automotive markets. Our design uses the Xilinx Spartan-3 low-cost FPGA as a baseline and achieves substantial power savings through a series of power optimizations. The resulting architecture is compatible with existing commercial design tools. The implementation is done in a 90nm triple-oxide CMOS process. Compared to the baseline design, Pika consumes 46% less active power and 99% less standby power. Furthermore, it retains circuit and configuration state during standby mode, and wakes up from standby mode in approximately 100ns.
105 A Simulator for Designing an Elevator with a Reduced-Vibration Structure (2002)

We have developed a simulator for evaluating the cage vertical vibration of an elevator. It enables an engineer to evaluate the cage vibration in the design stage of an elevator. The simulator is composed of an elevator mechanical model and a controller model. It can evaluate the cage vibration as the cage moves in the hoistway. It thus allows the cage vibration of a design to be checked before production, and the elevator structure can be re-designed to reduce the cage vibration if the estimated cage vibration is too large. As a result, the need for actual elevator vibration testing can be reduced.
NIPS 2016 Workshop on Representation Learning in Artificial and Biological Neural Networks (MLINI 2016) (2017)

This workshop explores the interface between cognitive neuroscience and recent advances in AI fields that aim to reproduce human performance such as natural language processing and computer vision, and specifically deep learning approaches to such problems. When studying the cognitive capabilities of the brain, scientists follow a system identification approach in which they present different stimuli to the subjects and try to model the response that different brain areas have of that stimulus. The goal is to understand the brain by trying to find the function that expresses the activity of brain areas in terms of different properties of the stimulus. Experimental stimuli are becoming increasingly complex with more and more people being interested in studying real life phenomena such as the perception of natural images or natural sentences. There is therefore a need for a rich and adequate vector representation of the properties of the stimulus, that we can obtain using advances in machine learning. In parallel, new ML approaches, many of which in deep learning, are inspired to a certain extent by human behavior or biological principles. Neural networks for example were originally inspired by biological neurons. More recently, processes such as attention are being used which have are inspired by human behavior. However, the large bulk of these methods are independent of findings about brain function, and it is unclear whether it is at all beneficial for machine learning to try to emulate brain function in order to achieve the same tasks that the brain achieves.
MODELING OF CHIP BED PACKING IN A CONTINUOUS KRAFT COOKING DIGESTER (2008)

This work focused on modeling of the chip bed packing phenomena in a continuous kraft cooking digester. A better understanding of chip bed packing would make it possible to optimize chip flow conditions in the digester, thereby ensuring uniform fiber quality and production efficiency. &#13;\n Chips are fed continuously into the digester, with the chip flow forming a solid bed. As the solid chip bed moves slowly downwards, cooking reactions proceed, which leads to softening of the chips. The softening of chips and the process conditions, flows and gravitational, are major variables affecting the chip bed packing. A new computer model, TKK Packing Simulator, was created to study the chip bed packing in a continuous digester. The simulator was verified against mill-scale conditions by conducting measurements in a continuous cooking plant. &#13;\n The packing simulator was found to give an accurate picture of the process flows inside the continuous digester. As digesters have grown bigger, controlling the liquor flows in the chip bed has become increasingly important. A tracer test was used to verify the liquor flow, which can be far from ideal in a modern digester. &#13;\n It is important to have optimal packing and flow conditions inside the digester, because too high packing and channeling of the liquor flow leads to non-uniform cooking, production disturbances and impaired fiber quality. The simulator developed in the present research can be used to determine optimal packing and flow conditions.
Quantitative investigation of geometrical axon guidance via PDMS microstructures for small-scale well-defined neural networks. (2018)

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Supplementary Figure 5 from Efficacy of Levo-1-Methyl Tryptophan and Dextro-1-Methyl Tryptophan in Reversing Indoleamine-2,3-Dioxygenase–Mediated Arrest of T-Cell Proliferation in Human Epithelial Ovarian Cancer (2023)

Supplementary Figure 5 from Efficacy of Levo-1-Methyl Tryptophan and Dextro-1-Methyl Tryptophan in Reversing Indoleamine-2,3-Dioxygenase–Mediated Arrest of T-Cell Proliferation in Human Epithelial Ovarian Cancer
Analysis of variation in mouse TPMT genotype, expression and activity (2004)

Although the mouse has great potential for pharmacogenomic discovery, little is known about variation in drug response or genetic variation in pharmacologically relevant genes between inbred mouse strains. We therefore assessed variation in gene sequence, mRNA expression and protein activity of thiopurine methyltransferase (TPMT) in multiple inbred mouse strains. TPMT activity was measured by high-performance liquid chromatography detection of 6-MMP produced by incubation of liver homogenates with 6-MP. Genetic variation was assessed by resequencing and single nucleotide polymorphism (SNP) genotyping using pyrosequencing technology. mRNA expression was measured by real-time polymerase chain reaction. We observed an almost five-fold variation in TPMT activity, with strains falling into distinct low and high activity groups. This pattern of TPMT activity was highly correlated with expression of TPMT mRNA among strains, and high TPMT expression is dominant in F1 hybrids. To correlate genotype with phenotype, 29 SNPs and one insertion/deletion were genotyped throughout the TPMT gene and upstream 10 kb. Only two haplotypes were observed across all 30 polymorphisms, corresponding to the low and high activity groups. These results suggest that differential mouse TPMT activity is due to variation in mRNA expression. In addition, the identified pattern of low haplotype diversity suggests that the mouse is likely to be useful for pharmacogenomic discovery by associating haplotype blocks with drug response phenotypes among inbred strains.
Ionic Liquids for Electrolyte-Gating of ZnO Field-Effect Transistors (2012)

We investigate the influence of the chemical structure of a range of imidazolium-based ionic liquids (IL) on their properties as electrolytes and the device characteristics of electrolyte-gated field-effects transistors (FETs) based on spray-deposited polycrystalline zinc oxide (ZnO). We find a decrease of electron field-effect mobility that correlates with the capacitance of the ionic liquids and not only with the size of the IL-cation. The device stability depends significantly on testing conditions. While they are reasonably stable in nitrogen, ZnO-FETs degrade rapidly in ambient air due to absorption of water by the IL and the resulting ZnO surface reactions. Replacement of the most acidic hydrogen atom of the imidazolium cation and surface passivation of ZnO with hexamethyldisilazane improve environmental stability.
Optofluidic Grating Spectrograph on a Chip (2009)

We demonstrated liquid metal based optical components such as mirrors and reflection gratings for building on-chip optofluidic spectrographs and monochromators. We designed a Czerny-Turner spectrograph with 1.7nm resolution, 200nm FSR and a footprint of 3cm by 3cm.
Quantification of the Impact of the HIV-1-Glycan Shield on Antibody Elicitation (2017)

While the HIV-1-glycan shield is known to shelter Env from the humoral immune response, its quantitative impact on antibody elicitation has been unclear. Here, we use targeted deglycosylation to measure the impact of the glycan shield on elicitation of antibodies against the CD4 supersite. We engineered diverse Env trimers with select glycans removed proximal to the CD4 supersite, characterized their structures and glycosylation, and immunized guinea pigs and rhesus macaques. Immunizations yielded little neutralization against wild-type viruses but potent CD4-supersite neutralization (titers 1: >1,000,000 against four-glycan-deleted autologous viruses with over 90% breadth against four-glycan-deleted heterologous strains exhibiting tier 2 neutralization character). To a first approximation, the immunogenicity of the glycan-shielded protein surface was negligible, with Env-elicited neutralization (ID<sub>50</sub>) proportional to the exponential of the protein-surface area accessible to antibody. Based on these high titers and exponential relationship, we propose site-selective deglycosylated trimers as priming immunogens to increase the frequency of site-targeting antibodies.
Mechanism of Asymmetric Hydrogenation of β-Dehydroamino Acids Catalyzed by Rhodium Complexes: Large-Scale Experimental and Computational Study (2013)

The mechanism of asymmetric hydrogenation of five representative β-dehydroamino acids catalyzed by rhodium complexes of (R)-(tert-butylmethylphosphino)(di-tert-butylphosphino)methane (trichickenfootphos, TCFP) and (R,R)-1,2-bis(tert-butylmethylphosphino)benzene (BenzP*) was studied through a combination of extensive NMR experiments and state-of-the-art DFT computations in order to reveal the crucial factors governing the sense and order of enantioselectivity in this industrially important reaction. The binding mode of the substrate with a Rh(I) catalyst was found to be highly dependent on the nature of the rhodium complex and the substrate. Thus, no substrate binding was detected for [Rh((R,R)-BenzP*)S2]+SbF6– (5) and (E)-3-acetylamino-2-butenoate (2a) even at 173 K. [Rh((R)-TCFP) S2]+BF4– (3) exhibited weak reversible binding with 2a in the temperature interval 173–253 K with the formation of complex 4a, whereas at ambient temperature, slow isomerization of 2a to (Z)-3-acetylamino-2-butenoate (2b) took place. The investigations with a total of 10 combinations of the catalysts and substrates demonstrated various binding modes that did not affect significantly the enantioselectivities observed in corresponding catalytic reactions and in low temperature hydrogenations of the catalyst–substrate complexes. The monohydride intermediate 10 formed quantitatively when the equilibrium mixture of 2a, 3, and 4a was hydrogenated at 173 K. Its molecular structure including relative stereochemistry was determined by NMR experiments. These results together with the stereochemichal outcome of the low-temperature hydrogenation (99.2% ee, R) and DFT calculations led to the reasonable reaction pathway of the asymmetric hydrogenation of 2a catalyzed by 3. The conceivable catalytic pathways were computed for five combinations of the BenzP*-Rh catalyst and prochiral β-dehydroamino acids 2a,b and 21–23. In most cases, it was found that the pathways involving the hydrogenation of Rh(I) square planar chelate complexes are usually higher in free energy than the pathways with the hydrogen activation prior to the chelate formation. Computed differences in the free energies of the transition states for the double bond coordination stage of the R and S pathways reasonably well reproduce the optical yields observed experimentally in the corresponding catalytic reactions and in the low temperature hydrogenation experiments. To explain extremely high ee’s (>99% ee) in some of the hydrogenations, it is necessary to analyze in more detail the participation of the solvent in the enantiodetermining step.
What is formal verification? (2005)

Formal verification is the use of mathematical techniques to ensure that a design conforms to some precisely expressed notion of functional correctness. Concretely, assume that you have (1) a model of a design, (2) some description of the environment that the design is supposed to operate in, and (3) some properties that the design is intended to fulfill. Given this information, you may want to search for some input patterns that the environment could generate that will violate the properties. Classical approaches to demonstrating that such input stimuli exist are random simulation, or directed test. Formal verification is an alternative approach that can be used both to search for inputs sequences that violate the properties, and prove that the properties always hold in the case when no such stimuli exist.Formal verification can be applied to designs described at many different levels of abstraction, ranging from the gate level, to RTL implementations, and in some cases even to transaction level models described in standardized programming languages.There are several different use models for formal verification. Some design teams use it to boost the coverage of random simulation and hunt for bugs, whereas others make full blown use of it to conclusively prove that certain properties hold. State-of-the-art tools integrate formal verification engines with simulation in a seamless way.A particular formal verification problem of great interest in EDA is equivalence checking. Here, the property that is checked is whether two different designs always have the same input/output behavior with respect to some notion of equivalence. Special algorithms are used when it is known that the two designs differ only in restricted ways, for example when combinational optimization only has been used to derive one from the other.Compute resources required by formal verification algorithms generally grow very quickly as design sizes increase. Current formal verification research aims to increase the capacity of the design analysis algorithms, and to make formal verification usable earlier in the design cycle. For equivalence checking, hot topics include better capacity for data path verification and support for verification of sequential transformations.
What can I say? (1998)

This paper presents experimental results comparing two different designs for a spoken language interface to entail. We compare a mixed-initiative dialogue style, in which users can flexibly control the dialogue, to a systemiuitiative dialogue style, in which the system controls the dialogue. Our results show that even though the mixedinitiative system is more eflicient, as measured by number of turns, or elapsed time to complete a set of email tasks, users prefer the system-initiative interface. We posit that these preferences arise from the fact that the system initiative inter&e is easier to learn and more predictable.