gebhart/patrepeval huggingface dataset:
The advent of de novo proteins for cancer immunotherapy (2020)

Engineered proteins are revolutionizing immunotherapy, but advances are still needed to harness their full potential. Traditional protein engineering methods use naturally existing proteins as a starting point, and therefore, are intrinsically limited to small alterations of a protein's natural structure and function. Conversely, computational de novo protein design is free of such limitation, and can produce a virtually infinite number of novel protein sequences, folds, and functions. Recently, we used de novo protein engineering to create Neoleukin-2/15 (Neo-2/15), a protein mimetic of the function of both interleukin-2 (IL-2) and interleukin-15 (IL-15). To our knowledge, Neo-2/15 is the first de novo protein with immunotherapeutic activity, and in murine cancer models, it has demonstrated enhanced therapeutic potency and reduced toxicity compared to IL-2. De novo protein design is already showcasing its tremendous potential for driving the next wave of protein-based therapeutics that are explicitly engineered to treat disease.
Kinetic Mechanism of Ligand Binding in Human Ileal Bile Acid Binding Protein as Determined by Stopped-Flow Fluorescence Analysis (2007)

Cooperative ligand binding to human ileal bile acid binding protein (I-BABP) was studied using the stopped-flow fluorescence technique. The kinetic data obtained for wild-type protein are in agreement with a four-step mechanism where after a fast conformational change on the millisecond time scale, the ligands bind in a sequential manner, followed by another, slow conformational change on the time scale of seconds. This last step is more pronounced in the case of glycocholate (GCA), the bile salt that binds with high positive cooperativity and is absent in mutant I-BABP proteins that lack positive cooperativity in their bile salt binding. These results suggest that positive cooperativity in human I-BABP is related to a slow conformational change of the protein, which occurs after the second binding step. Analogous to that in the intestinal fatty acid binding protein (I-FABP), we hypothesize that ligand binding in I-BABP is linked to a disorder-order transition between an open and a closed form of the protein.
Ferromagnetic Switching of Knotted Vector Fields in Liquid Crystal Colloids (2015)

We experimentally realize polydomain and monodomain chiral ferromagnetic liquid crystal colloids that exhibit solitonic and knotted vector field configurations. Formed by dispersions of ferromagnetic nanoplatelets in chiral nematic liquid crystals, these colloidal ferromagnets exhibit spontaneous long-range alignment of magnetic dipole moments of individual platelets, giving rise to a continuum of the magnetization field M(r). Competing effects of surface confinement and chirality prompt spontaneous formation and enable the optical generation of localized twisted solitonic structures with double-twist tubes and torus knots of M(r), which exhibit a strong sensitivity to the direction of weak magnetic fields ∼1 mT. Numerical modeling, implemented through free energy minimization to arrive at a field-dependent three-dimensional M(r), shows a good agreement with experiments and provides insights into the torus knot topology of observed field configurations and the corresponding physical underpinnings.
Exploring Indicators of Digital Self-Harm with Eating Disorder Patients (2019)

Digital self-harm encompasses a variety of activities, including the use of social media to facilitate or amplify mental illness-related behaviors. To understand the extent of these behaviors and their impacts, we conducted an in-depth case study with three patients who are in recovery from an eating disorder. We collected survey data, conducted interviews reflecting back to their technology use during their active disease state, and reviewed up to 18 months of their social media data leading up to the start of their initial point of recovery. Through the triangulation of this data, we explore the role of social media and social technologies in relation to their eating disorder. By utilizing this methodology, we were able to provide a contextually rich and nuanced lens for exploring the impacts of digital self-harm on this group of patients. We found that patients acknowledged that the eating disordered content on social media had a negative impact on their health, often contributing to a worsening of the physical manifestations of their disorder. Conversely, while they actively consumed this content, our participants did not produce online content related to eating disordered activities or behaviors. Finally, we discuss the patterns within their social media data and how platform designers and operators could use these findings in the future through design considerations for future platform-based interventions.
CO2 Leakage from Heterogeneous Storage Formations (2010)

Abstract After injection of CO2 into the subsurface formation, various storage mechanisms help immobilize CO2 in the porous medium. Injection strategies that promote the buoyant movement of CO2 after injection can increase immobilization by the mechanisms of dissolution and residual phase trapping. In a heterogeneous storage formation where capillary entry pressure of the rock is correlated with other petrophysical properties, numerous local capillary barriers exist and can trap rising CO2 below them. In this work, we study the effect of these barriers on CO2 leakage from the storage formation. We first introduce a no-risk-of-leakage scenario for storage, which sets an upper bound on the amount of CO2 that can be stored without contacting the overlying seal. Accounting for capillary heterogeneity reduces this upper bound. In practice operators are likely to seek to store more CO2 than the no-risk-of-leakage bound in any given reservoir. Thus we also examine the form of the gas cap established by the rising CO2 plume, and we simulate leakage from this gas cap through the top seal. Our leakage scenario is simulated in different cases with homogeneous and heterogeneous capillary pressure field, and CO2 trapping is quantified based on the results of the leakage. Capillary heterogeneity is introduced via Leverett scaling group. A new parameter called security index is also defined to quantify the risk of leakage. Finally, the statistics of the local capillary barriers are used to find a probability distribution of leakage amounts from the storage formation. We conclude that ignoring heterogeneity gives the worst case estimate of the risk. Local capillary trapping reduces potential leakage through failed seal, but a range of CO2 leakage amounts can occur depending on heterogeneity and location of leak. The thickness of the sealing layer and the presence of an active open aquifer connected to the leak do not change the leakage volume of CO2. A probabilistic approach based on statistics of local capillary barriers can be used to analyze the risk associated with leakage.
Cloning, expression, and characterization of human apolipoprotein(a) kringle IV37. (1994)

A portion of kringle IV37 (KIV37) of apolipoprotein (a), (apo(a)), was polymerase chain reaction-cloned from human liver cDNA. The protein product of this clone was expressed in Escherichia coli as a poly histidine fusion protein. Based on recovery of purified fusion apo(a) KIV37 protein expression levels were estimated to be 10 mg/g of E. coli cell paste. Mass spectral analysis showed the molecular mass of fusion apo(a) KIV37 to be 12,260 +/- 1 daltons. Almost all fusion apo(a) KIV37 was expressed as inclusion bodies and had to be refolded. Fusion apo(a) KIV37 was isolated from the inclusion bodies and purified by lysine-Sepharose affinity chromatography by eluting with 0.2 M epsilon-aminocaproic acid. The fusion protein was treated with thrombin to yield a homogeneous, functional apo(a) KIV37 domain composed of 92 amino acids having a molecular mass of 10,510 +/- 1 daltons. N-terminal protein sequencing and amino acid analysis have confirmed the sequence and composition of apo(a) KIV37. The molar extinction coefficient, epsilon, for apo(a) KIV37 was determined to be 3.1 x 10(4) M-1 cm-1, and the pI was measured to be 6.7 +/- 0.1. In addition, the dissociation constants, Kd, for a series of 11 lysine analogs have been determined by measuring the change in intrinsic fluorescence of apo(a) KIV37 upon saturable binding with these compounds. Kd values ranged from 4.2 +/- 0.9 microM for trans-4-(aminomethyl)cyclohexanecarboxylic acid to 4.6 +/- 0.4 mM for L-arginine. Apo(a) KIV37 binds to plasmin-treated fibrinogen with an EC50 value of 14 +/- 1.2 microM and prevents the binding of Lp(a) to plasmin-treated fibrinogen with an IC50 value of 16 +/- 6 microM. Lp(a) binds to the plasmin-treated fibrinogen surface with an EC50 value of approximately 1.0 +/- 0.3 nM. These studies demonstrate that apo(a) KIV37 can be expressed at high levels, refolded properly, and used as a fully functional lysine-binding domain. In addition, these results also demonstrate that apo(a) KIV37 provides the major interaction of Lp(a) with fibrinogen. One additional weak binding site in Lp(a) is adequate to describe overall Lp(a) binding to fibrinogen.
Data from Expression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation (2023)

&lt;div&gt;AbstractPurpose:&lt;p&gt;Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Our recent preclinical work has suggested that PD-1/PD-L1 plays an important immunoregulatory role to limit effective antitumor T-cell responses induced by active immunotherapy. However, little is known about the functional role that PD-1 plays on human T lymphocytes in patients with malignant glioma.&lt;/p&gt;&lt;p&gt;&lt;b&gt;Experimental Design:&lt;/b&gt; In this study, we examined the immune landscape and function of PD-1 expression by T cells from tumor and peripheral blood in patients with malignant glioma.&lt;/p&gt;Results:&lt;p&gt;We found several differences between PD-1&lt;sup&gt;+&lt;/sup&gt; tumor-infiltrating lymphocytes (TIL) and patient-matched PD-1&lt;sup&gt;+&lt;/sup&gt; peripheral blood T lymphocytes. Phenotypically, PD-1&lt;sup&gt;+&lt;/sup&gt; TILs exhibited higher expression of markers of activation and exhaustion than peripheral blood PD-1&lt;sup&gt;+&lt;/sup&gt; T cells, which instead had increased markers of memory. A comparison of the T-cell receptor variable chain populations revealed decreased diversity in T cells that expressed PD-1, regardless of the location obtained. Functionally, peripheral blood PD-1&lt;sup&gt;+&lt;/sup&gt; T cells had a significantly increased proliferative capacity upon activation compared with PD-1&lt;sup&gt;−&lt;/sup&gt; T cells.&lt;/p&gt;Conclusions:&lt;p&gt;Our evidence suggests that PD-1 expression in patients with glioma reflects chronically activated effector T cells that display hallmarks of memory and exhaustion depending on its anatomic location. The decreased diversity in PD-1&lt;sup&gt;+&lt;/sup&gt; T cells suggests that the PD-1–expressing population has a narrower range of cognate antigen targets compared with the PD-1 nonexpression population. This information can be used to inform how we interpret immune responses to PD-1–blocking therapies or other immunotherapies.&lt;/p&gt;&lt;/div&gt;
Optimal input signal distribution and per-sample mutual information for nondispersive nonlinear optical fiber channel in large SNR limit (2015)

We consider a model nondispersive nonlinear optical fiber channel with additive white Gaussian noise at large $\mathrm{SNR}$ (signal-to-noise ratio) in the intermediate power region. Using Feynman path-integral technique we for the first time find the optimal input signal distribution maximizing the channel's per-sample mutual information. The finding of the optimal input signal distribution allows us to improve previously known estimates for the channel capacity. The output signal entropy, conditional entropy, and per-sample mutual information are calculated for Gaussian, half-Gaussian and modified Gaussian input signal distributions. We explicitly show that in the intermediate power regime the per-sample mutual information for the optimal input signal distribution is greater than the per-sample mutual information for the Gaussian and half-Gaussian input signal distributions.
Empirical evaluation of defect projection models for widely-deployed production software systems (2004)

Defect-occurrence projection is necessary for the development of methods to mitigate the risks of software defect occurrences. In this paper, we examine user-reported software defect-occurrence patterns across twenty-two releases of four widely-deployed, business-critical, production, software systems: a commercial operating system, a commercial middleware system, an open source operating system (OpenBSD), and an open source middleware system (Tomcat). We evaluate the suitability of common defect-occurrence models by first assessing the match between characteristics of widely-deployed production software systems and model structures. We then evaluate how well the models fit real world data. We find that the Weibull model is flexible enough to capture defectoccurrence behavior across a wide range of systems. It provides the best model fit in 16 out of the 22 releases. We then evaluate the ability of the moving averages and the exponential smoothing methods to extrapolate Weibull model parameters using fitted model parameters from historical releases. Our results show that in 50% of our forecasting experiments, these two naïve parameter-extrapolation methods produce projections that are worse than the projection from using the same model parameters as the most recent release. These findings establish the need for further research on parameter-extrapolation methods that take into account variations in characteristics of widely-deployed, production, software systems across multiple releases. <br><br>
Dubins Path Guidance for Fixed-Wing UAS Remote Sensing Applications (2020)

In this work, real-time optimal path planning is achieved for flight line tracking and loiter circles by taking into account dynamic constraints of a fixed-wing unmanned aircraft using Dubins path generation. Next, adaptive guidance algorithms are applied in order for the aircraft to precisely track these optimal paths. Flight line tracking is improved through the use of a trackline integral acceleration term, and optimal control techniques are applied using an augmented state space model. Improvements in aircraft tracking performance compared to traditional methods is quantified through simulations utilizing six-degree of freedom aircraft equations of motion for various flight line survey missions.
The Impact of Deadline Misses on the Control Performance of High-End Motion Control Systems (2015)

In high-end motion control systems, the real-time computational platform must execute tasks from multiple control loops operating at high sampling rates. In recent years, traditional special-purpose platforms have been replaced by general-purpose multiprocessor platforms, which introduce significant fluctuations in execution times. While considering worst-case execution times would severely reduce the sampling rates, accepting deadline misses and assuring that the control system still meets the desired specifications is challenging. In this paper, we provide a framework to model and assert the impact of deadline misses in a real-time control loop. We consider stochastic models for deadline misses and characterize the mean and the variance of closed-loop output variables based on a time-domain analysis. We illustrate the usefulness of our framework in the control of a benchmark motion control experimental setup and in the control of a wafer stage in a lithographic machine.
Far-UVC light efficiently and safely inactivates airborne human coronaviruses (2020)

Abstract A direct approach to limit airborne transmission of pathogens is to inactivate them within a short time of their production. Germicidal ultraviolet light (UV), typically at 254 nm, is effective in this context, but it is a health hazard to the skin and eyes. By contrast, far-UVC light (207-222 nm) efficiently kills pathogens without harm to exposed human cells or tissues. We previously demonstrated that 222-nm UV light efficiently kills airborne influenza virus (H1N1); here we extend the far-UVC studies to explore efficacy against human coronaviruses from subgroups alpha (HCoV-229E) and beta (HCoV-OC43). We found that low doses of, respectively 1.7 and 1.2 mJ/cm 2 inactivated 99.9% of aerosolized alpha coronavirus 229E and beta coronavirus OC43. Based on these results for the beta HCoV-OC43 coronavirus, continuous far-UVC exposure in public locations at the currently recommended exposure limit (3 mJ/cm 2 /hour) would result in 99.9% viral inactivation in ~ 25 minutes. Increasing the far- UVC intensity by, say, a factor of 2 would halve these disinfection times, while still maintaining safety. As all human coronaviruses have similar genomic size, a key determinant of radiation sensitivity, it is realistic to expect that far-UVC light will show comparable inactivation efficiency against other human coronaviruses, including SARS-CoV-2.
Spectral clustering in peptidomics studies helps to unravel modification profile of biologically active peptides and enhances peptide identification rate (2009)

When studying the set of biologically active peptides (the so-called peptidome) of a cell type, organ, or entire organism, the identification of peptides is mostly attempted by MS. However, identification rates are often dismally unsatisfactory. A great deal of failed or missed identifications may be attributable to the wealth of modifications on peptides, some of which may originate from in vivo post-translational processes to activate the molecule, whereas others could be introduced during the tissue preparation procedures. Preliminary knowledge of the modification profile of specific peptidome samples would greatly improve identification rates. To this end we developed an approach that performs clustering of mass spectra in a way that allows us to group spectra having similar peak patterns over significant segments. Comparing members of one spectral group enables us to assess the modifications (expressed as mass shifts in Dalton) present in a peptidome sample. The clustering algorithm in this study is called Bonanza, and it was applied to MALDI-TOF/TOF MS spectra from the mouse. Peptide identification rates went up from 17 to 36% for 278 spectra obtained from the pancreatic islets and from 21 to 43% for 163 pituitary spectra. Spectral clustering with subsequent advanced database search may result in the discovery of new biologically active peptides and modifications thereof, as shown by this report indeed.
Improving the Selectivity of an Osseointegrated Neural Interface: Proof of Concept For Housing Sieve Electrode Arrays in the Medullary Canal of Long Bones (2021)

Sieve electrodes stand poised to deliver the selectivity required for driving advanced prosthetics but are considered inherently invasive and lack the stability required for a chronic solution. This proof of concept experiment investigates the potential for the housing and engagement of a sieve electrode within the medullary canal as part of an osseointegrated neural interface (ONI) for greater selectivity toward improving prosthetic control. <i>The working hypotheses</i> are that (A) the addition of a sieve interface to a cuff electrode housed within the medullary canal of the femur as part of an ONI would be capable of measuring efferent and afferent compound nerve action potentials (CNAPs) through a greater number of channels; (B) that signaling improves over time; and (C) that stimulation at this interface generates measurable cortical somatosensory evoked potentials through a greater number of channels. The modified ONI was tested in a rabbit (<i>n</i> = 1) amputation model over 12 weeks, comparing the sieve component to the cuff, and subsequently compared to historical data. Efferent CNAPs were successfully recorded from the sieve demonstrating physiological improvements in CNAPs between weeks 3 and 5, and somatosensory cortical responses recorded at 12 weeks postoperatively. This demonstrates that sieve electrodes can be housed and function within the medullary canal, demonstrated by improved nerve engagement and distinct cortical sensory feedback. This data presents the conceptual framework for housing more sophisticated sieve electrodes in bone as part of an ONI for improving selectivity with percutaneous connectivity toward improved prosthetic control.
β-Adrenergic receptors are involved in histamine-induced secretion of proopiomelanocortin-derived peptides and prolactin in rats (1995)

The neurotransmitter histamine (HA) is involved in central regulation of secretion of prolactin (PRL) and the proopiomelanocortin (POMC)-derived peptides adrenocorticotropin (ACTH), beta-endorphin (beta-END) and alpha-melanocyte-stimulating hormone (alpha-MSH). The effect of HA on POMC-derived peptides and PRL release is, at least in part, indirect and may involve activation of catecholaminergic systems. Therefore, we investigated the effect of beta-adrenergic receptor blockade on HA or HA agonist-induced release of ACTH, beta-END, alpha-MSH and PRL. Central administration of HA, the H1-receptor agonist 2-thiazolylethylamine (2-TEA) or the H2-receptor agonist 4-methylhistamine (4-MeHA) stimulated the secretion of ACTH, beta-END, alpha-MSH and PRL. Pretreatment with the beta-adrenergic antagonist propranolol inhibited secretion of the POMC peptides in response to HA, 2-TEA or 4-MeHA. Propranonol only inhibited the PRL response to HA or 2-TEA, but had no effect on the PRL response to 4-MeHA. Administration of the beta-receptor agonist isoproterenol stimulated ACTH, beta-END, alpha-MSH and PRL two to five-fold. This effect was totally blocked by pretreatment with propranolol. We conclude that HA-induced secretion of POMC-derived peptides from the anterior and intermediate lobe of the pituitary gland and of PRL from the anterior lobe is, at least in part, mediated via catecholamines. beta-Adrenergic receptors are involved in the mediation of the POMC response to H1- as well as H2-receptor activation, whereas beta-receptors are involved only in the mediation of the PRL response to H1-receptor activation.
Lipid- and Polymer-Based Nanostructures for Cancer Theranostics (2012)

The relatively new field of nanotheranostics combines the advantages of in vivo diagnosis with the ability to administer treatment through a single nano-sized carrier, offering new opportunities for cancer diagnosis and therapy. Nanotheranostics has facilitated the development of nanomedicine through direct visualization of drug blood circulation and biodistribution. From a clinical perspective, nanotheranostics allows therapies to be administered and monitored in real time, thus decreasing the potential of under- or over-dosing and allowing for more personalized treatment regimens. Herein, we review recent development of nanotheranostics using lipid- and polymer-based formulations, with a particular focus on their applications in cancer research. Recent advances in nanotechnology aimed to combine therapeutic molecules with imaging agents for magnetic resonance imaging, radionuclide imaging, or fluorescence imaging are discussed.
Wear Mechanisms in Grinding of PCBN (2015)

PCBN-inserts have a high potential in the cutting of hardened steel, cast iron and super alloys due to their high hardness and heat resistance. Nevertheless they have a high purchase price, which lowers the economic benefits for the end user compared to other cutting materials. This is caused by the high production costs of the inserts. The grinding of PCBN-inserts causes a major proportion of these costs as a result of the high grinding wheel wear. The primary wear mechanism is grain breakout followed by clogging of the grinding layer. This study shows that the efficiency of the grinding process can be increased significantly by applying low cutting speeds and high feed rates. In this case, splintering of the grinding grain is the main wear mechanism.