gebhart/patrepeval huggingface dataset:
Unraveling the Effect of Immunogenicity on the PK/PD, Efficacy, and Safety of Therapeutic Proteins (2016)

Biologics have emerged as a powerful and diverse class of molecular and cell-based therapies that are capable of replacing enzymes, editing genomes, targeting tumors, and more. As this complex array of tools arises a distinct set of challenges is rarely encountered in the development of small molecule therapies. Biotherapeutics tend to be big, bulky, polar molecules comprised of protein and/or nucleic acids. Compared to their small molecule counterparts, they are fragile, labile, and heterogeneous. Their biodistribution is often limited by hydrophobic barriers which often restrict their administration to either intravenous or subcutaneous entry routes. Additionally, their potential for immunogenicity has proven to be a challenge to developing safe and reliably efficacious drugs. Our discussion will emphasize immunogenicity in the context of therapeutic proteins, a well-known class of biologics. We set out to describe what is known and unknown about the mechanisms underlying the interplay between antigenicity and immune response and their effect on the safety, efficacy, pharmacokinetics, and pharmacodynamics of these therapeutic agents.
Cell Patterning Method Using Resonance Vibration of a Metallic Cell Cultivation Substrate (2016)

Spatial control of cell position is essential for numerous studies in tissue engineering, such as generation of linearly patterned muscle tissues, radially patterned liver lobule tissues, and circularly formed anal sphincter. This study proposes a novel method capable of patterning cells in a certain shape on a cell cultivation substrate. The concept is to pattern cells along the nodal position of resonance vibration on a cell cultivation substrate. Note that there are numerous resonance vibrations with different nodal patterns. In this study, we constructed a cell cultivation device consisting of a metallic cell cultivation substrate that can be excited to generate resonance vibration using a piezoelectric ceramic disk glued to the back of the substrate. In this study, we generated resonance vibration with a cross-circle nodal pattern. The cultivation substrate was a ø40 mm × 1 mm stainless steel plate, and the resonance frequency of the vibration was 21.4 kHz. Using the device, we conducted cell patterning experiments employing calf chondrocytes using various vibration amplitudes (1.0, 1.5, and 2.0 µmp-p). Cells were cultured for 2 hours. After the experiment, the cell density distribution on the substrate was measured by staining viable cells with calcein. Additionally, we confirmed the viability of the patterned cells after exposure to acoustic pressure produced by the resonance vibration by counting the number of cells attached to the substrate. Viable cells were successfully patterned along the nodal position when the vibration amplitude was 1.5 µmp-p. The number of cells attached to the substrate was 99.2% of that without vibration. Conversely, when the amplitude was 1.0 µmp-p, the cells were not patterned. The acoustic pressure produced by 1.0-µmp-p vibration was not large enough to move cells. Similarly, the cells could not be patterned when the amplitude was 2.0 µmp-p. In this case, flow of the culture medium induced by the high acoustic pressure probably prevented the cells from patterning. In conclusion, cells can be patterned along the nodal position of resonance vibration generated with an appropriate vibration amplitude. We believe that this method has great potential for use in tissue engineering.
Telomestatin and Diseleno Sapphyrin Bind Selectively to Two Different Forms of the Human Telomeric G-Quadruplex Structure (2005)

The human telomeric sequence d[T(2)AG(3)](4) has been demonstrated to form different types of G-quadruplex structures, depending upon the incubation conditions. For example, in sodium (Na(+)), a basket-type G-quadruplex structure is formed. In this investigation, using circular dichroism (CD), biosensor-surface plasmon resonance (SPR), and a polymerase stop assay, we have examined how the addition of different G-quadruplex-binding ligands affects the conformation of the telomeric G-quadruplex found in solution. The results show that while telomestatin binds preferentially to the basket-type G-quadruplex structure with a 2:1 stoichiometry, 5,10,15,20-[tetra-(N-methyl-3-pyridyl)]-26-28-diselena sapphyrin chloride (Se2SAP) binds to a different form with a 1:1 stoichiometry in potassium (K(+)). CD studies suggest that Se2SAP binds to a hybrid G-quadruplex that has strong parallel and antiparallel characteristics, suggestive of a structure containing both propeller and lateral, or edgewise, loops. Telomestatin is unique in that it can induce the formation of the basket-type G-quadruplex from a random coil human telomeric oligonucleotide, even in the absence of added monovalent cations such as K(+) or Na(+). In contrast, in the presence of K(+), Se2SAP was found to convert the preformed basket G-quadruplex to the hybrid structure. The significance of these results is that the presence of different ligands can determine the type of telomeric G-quadruplex structures formed in solution. Thus, the biochemical and biological consequences of binding of ligands to G-quadruplex structures found in telomeres and promoter regions of certain important oncogenes go beyond mere stabilization of these structures.
A New Approach to Evaluating the Risk–Benefit Equation for Dual-Use and Gain-of-Function Research of Concern (2018)

In the twenty-first century, biology faces a problem that has previously vexed other disciplines such as physics, namely the prospect that its knowledge domain could be used to generate biological agents with altered properties that enhanced their weapon potential. Biological weapons bring the additional dimension that these could be self-replicating, easy to manufacture and synthesized with commonly available expertise. This resulted in increasing concern about the type of research done and communicated, despite the fact that such research often has direct societal benefits, bringing the dual-use dilemma to biology. The conundrum of dual use research of concern was crystallized by the so-called "gain-of-function" type of experiments in which avian influenza viruses were endowed with new properties in the laboratory such as increased virulence and the capacity for mammalian transmission. After more than a decade of intensive discussion and controversy involving biological experiments with dual-use potential, there is no consensus on the issue except for the need to carry out such experiments in the safest conditions possible. In this essay, we review the topic with the hindsight of several years and suggest that instead of prescribing prohibitions and experimental limitations the focus should be on the importance of scientific questions at hand. We posit that the importance of a scientific question for medical and scientific progress provides a benchmark to determine the acceptable level of risk in biological experimentation.
Optica geometrica (2018)

La óptica geométrica estudia la formación de imágenes. La función de un sistema de lentes o espejos es recoger la radiación que parte del objeto y producir una imagen, que es una distribución de flujo similar al objeto sobre el plano imagen.
New approaches to security and availability for cloud data (2013)

Extending the data trust perimeter from the enterprise to the public cloud requires more than encryption.
Statistical approach utilizing neural networks for CD error prediction (2007)

We studied a three-layer backpropagation neural network to describe nonlinear relationships between inputs (error sources/control knobs) and output CDs. The application of the neural network to modeling of optical proximity effect for a 65nm node CMOS gate layer was investigated. The prediction accuracy of the neural network was improved with the increase in the training data size, becoming higher than that of a conventional lithography simulation with a lumped parameter model. The result suggests that neural networks trained with a sufficient amount of data can provide the same or higher accuracy for the CD error prediction than physical model-based approaches. The use of information of aerial images as input parameters improved the accuracy. Also, pattern density effects, which are difficult to treat by a conventional lithography simulation, could be successfully reflected in the CD error prediction. Using lot data over a period of time, we trained a neural network in which the exposure parameters and lot mean CDs were inputs and outputs, respectively. From the network, lot mean CDs for successive periods were able to be predicted. From these results, we conclude that the application of neural networks for CD control in advanced lithography is worth developing.
Coordinated multipoint - multiuser superposition transmission (2017)

Multi-user superposition transmission is recently standardized as DL-MUST for Rel. 13 (LTE-A Pro) and is shown to improve capacity as well as cell-edge user throughput performance. In this demo, we utilize the concept of multi-user superposition transmission to enable a simple coordinated multipoint transmission scheme. In contrast to regular DL-MUST, where one base station serves a pair of near- and far user, the component signals in our proposed scheme are transmitted from independent users to one base-station in the uplink. A phaseoffset estimation and signaling scheme is introduced in order to provide the required coordination feedback at the individual user sites such that the received composite signal aligns as a standard MUST - Cat. 1 signal. In our demo, channel measurements from are used to demonstrate the scheme in a hardware-in-the-loop framework.
ChemInform Abstract: Introduction of a Lipophilic Thioether Tether in the Minor Groove of Nucleic Acids for Antisense Applications. (1994)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Oxide Glass/Amorphous Metal Alloy Laminated Membrane for Hydrogen Separation (2009)

Abstract A five-layered membrane composed of an amorphous Ni–Nb–Zr alloy substrate (ca. 30 μm), thin proton–electron mixed conductive tungsten phosphate glass films (ca. 50 nm) and Ni coatings (ca. 20 nm) was fabricated by pulsed laser deposition and vacuum evaporation. A flux of hydrogen passed through the laminated membrane without Pd at 673 K at ca. 2×10−6 mol·cm−2·s−1, and no degradation was observed in the 10 h operation. The present results suggest that amorphous Ni–Nb–Zr alloy passivated with WO3-based oxide glass is a promising material for H2 filtering in a medium temperature range.
Synthesis and Antitumour Activity of New Derivatives of Flavone‐8‐acetic Acid (FAA). Part 2: Ring‐Substituted Derivatives (1997)

A range of 18 derivatives of flavone-8-acetic acid (FAA) with substituents on the 2-phenyl group have been prepared and their anti-tumour activity evaluated in vitro against a panel of human and murine tumour cell lines and in vivo against MAC 15A. There was no clear-cut relationship between in vitro and in vivo activity but the activity in each situation was found to be very sensitive to the precise substitution pattern with closely related isomers giving widely different activities. Some of the compounds, notably 10b,c,j, and r, were active in vivo and these require further studies in order to evaluate their potential for development.
Hepatitis C virus 3′UTR regulates viral translation through direct interactions with the host translation machinery (2013)

The 3' untranslated region (3'UTR) of hepatitis C virus (HCV) messenger RNA stimulates viral translation by an undetermined mechanism. We identified a high affinity interaction, conserved among different HCV genotypes, between the HCV 3'UTR and the host ribosome. The 3'UTR interacts with 40S ribosomal subunit proteins residing primarily in a localized region on the 40S solvent-accessible surface near the messenger RNA entry and exit sites. This region partially overlaps with the site where the HCV internal ribosome entry site was found to bind, with the internal ribosome entry site-40S subunit interaction being dominant. Despite its ability to bind to 40S subunits independently, the HCV 3'UTR only stimulates translation in cis, without affecting the first round translation rate. These observations support a model in which the HCV 3'UTR retains ribosome complexes during translation termination to facilitate efficient initiation of subsequent rounds of translation.
Advances in integrated magneto-optics (2003)

The integration of magneto-optical devices enables cost and size reduction in optical commutication systems. Nonreciprocal phase shifters can be used to build polarization independent isolators and circulators. New photonic bandgap materials with high Faraday rotation make conventional magneto-optic device concepts suitable for PLC integration. Keywords: isolators, circulators, nonreciprocal devices, integrated magneto-optics
Model-Free Learning and Optimal Policy Design in Multi-Agent MDPs Under Probabilistic Agent Dropout (2023)

This work studies a multi-agent Markov decision process (MDP) that can undergo agent dropout and the computation of policies for the post-dropout system based on control and sampling of the pre-dropout system. The central planner's objective is to find an optimal policy that maximizes the value of the expected system given a priori knowledge of the agents' dropout probabilities. For MDPs with a certain transition independence and reward separability structure, we assume that removing agents from the system forms a new MDP comprised of the remaining agents with new state and action spaces, transition dynamics that marginalize the removed agents, and rewards that are independent of the removed agents. We first show that under these assumptions, the value of the expected post-dropout system can be represented by a single MDP; this "robust MDP" eliminates the need to evaluate all $2^N$ realizations of the system, where N denotes the number of agents. More significantly, in a model-free context, it is shown that the robust MDP value can be estimated with samples generated by the pre-dropout system, meaning that robust policies can be found before dropout occurs. This fact is used to propose a policy importance sampling (IS) routine that performs policy evaluation for dropout scenarios while controlling the existing system with good pre-dropout policies. The policy IS routine produces value estimates for both the robust MDP and specific post-dropout system realizations and is justified with exponential confidence bounds. Finally, the utility of this approach is verified in simulation, showing how structural properties of agent dropout can help a controller find good post-dropout policies before dropout occurs.
Process intensification for the biological production of the fuel precursor butyric acid from biomass (2021)

The production of fuels from lignocellulosic biomass is key to reduce our reliance on petroleum and to promote a sustainable bioeconomy. Butyric acid (BA) is a promising chemical precursor for the production of renewable diesel and jet fuels. BA can be biologically produced from lignocellulosic sugars. However, challenges associated with product selectivity and recovery must be overcome to achieve industrially relevant metrics. Here, we evaluate various fermentation configurations and demonstrate near-homo-butyrate production by using the biocatalyst Clostridium tyrobutyricum. We also develop an advanced in situ product recovery process based on hybrid extraction-distillation (HED-ISPR) and conduct techno-economic analyses and life cycle assessments. We demonstrate that the HED-ISPR process lowers the overall capital and operating expenses and environmental impact compared to other traditional fermentation processes. Overall, BA minimum product selling price from biomass is 55% of the current BA selling price from petroleum, a significant decrease toward viable renewable fuel production.
On the Performance of Handover Mechanisms for Non-Terrestrial Networks (2022)

Next-generation wireless networks require massive connectivity and ubiquitous coverage, for which non-terrestrial networks (NTNs) are a promising enabler. However, NTNs, especially non-geostationary satellites bring about challenges such as increased handovers (HOs) due to the moving coverage area of the satellite on the ground. Accordingly, in this work, we compare the conventional measurement-based HO triggering mechanism with other alternatives such as distance, elevation angle, and timer-based methods in terms of the numbers of HOs, ping-pong HOs, and radio link failures. The system-level simulations, carried out in accordance with the 3GPP model, show that the measurement-based approach can outperform the other alternatives provided that appropriate values of hysteresis/offset margins and time-to-trigger parameters are used. Moreover, future directions regarding this work are also provided at the end.
Solution‐processed semitransparent p–n graphene oxide:CNT/ZnO heterojunction diodes for visible‐blind UV sensors (2011)

Abstract A high quality transparent p–n heterojunction device comprised of 1D zinc oxide (ZnO) nanorods (NRs) and an ultrathin 2D graphene oxide (GO):carbon nanotube (CNT) hybrid film was fabricated through a solution process. The turn on voltage and ideality factor of the device were 1.5 V and 6.1, respectively. Optical measurements revealed that the UV absorption of the ZnO NRs increased after a GO:CNT hybrid film was spray‐coated onto the NRs. As a result, the device exhibited a high response to UV illumination. The fabricated diode displayed high rectifying characteristics and excellent performance as a visible‐blind UV sensor.
Nanoparticle enabled optical fibers to side-emit germicidal ultraviolet light for biofilm control in water (2022)

Silica nanoparticle coating on 250 to 1000 um flexible quartz optical fiber facilitates side-emission of germicidal ultraviolet light (UV-C), which shows promise for disinfection of contaminated air, water, and surfaces. This work aims to develop an understanding of light interactions with the silica nanoparticles to allow more uniform side-emission of germicidal light along longer lengths of optical fibers. Two forms of light energy (refracted light and evanescent waves) are transmitted through optical fibers.
Phylogenetic debugging of a complete human biosynthetic pathway transplanted into yeast (2019)

Cross-species pathway transplantation enables insight into a biological process not possible through traditional approaches. We replaced the enzymes catalyzing the entire Saccharomyces cerevisiae adenine de novo biosynthesis pathway with the human pathway. While the 'humanized' yeast grew in the absence of adenine, it did so poorly. Dissection of the phenotype revealed that PPAT, the human ortholog of ADE4, showed only partial function whereas all other genes complemented fully. Suppressor analysis revealed other pathways that play a role in adenine de-novo pathway regulation. Phylogenetic analysis pointed to adaptations of enzyme regulation to endogenous metabolite level 'setpoints' in diverse organisms. Using DNA shuffling, we isolated specific amino acids combinations that stabilize the human protein in yeast. Thus, using adenine de novo biosynthesis as a proof of concept, we suggest that the engineering methods used in this study as well as the debugging strategies can be utilized to transplant metabolic pathway from any origin into yeast.
Geometric-phase-induced arbitrary polarization and orbital angular momentum generation in helically twisted birefringent photonic crystal fiber (2020)

The evolutions of polarization and orbital angular momentum (OAM) states of light in helically twisted birefringent photonic crystal fibers (TB-PCFs) are analyzed. It is shown that a circular polarization (CP) component ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="m1"> <mml:mrow> <mml:msub> <mml:mi>S</mml:mi> <mml:mn>3</mml:mn> </mml:msub> </mml:mrow> </mml:math> of a Stokes parameter) is periodically excited when usual linearly polarized (LP) modes of PCF are launched. The excitation originates from a geometric phase in TB-PCFs. The <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="m2"> <mml:mrow> <mml:msub> <mml:mi>S</mml:mi> <mml:mn>3</mml:mn> </mml:msub> </mml:mrow> </mml:math> excitation is larger for larger linear birefringence for a fixed twisting rate. If the linear birefringence is large enough, a CP filtering behavior can be seen in addition to the <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="m3"> <mml:mrow> <mml:msub> <mml:mi>S</mml:mi> <mml:mn>3</mml:mn> </mml:msub> </mml:mrow> </mml:math> excitation. From the analytical consideration of the sign of the geometric phase, the TB-PCF with periodical inversion of twisting is proposed to generate arbitrary polarization state on the Poincaré sphere. Next, an OAM state generation in multimode TB-PCFs is shown for higher-order LP mode input. By observing a far-field interference pattern from TB-PCF mixed with <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" display="inline" id="m4"> <mml:mrow> <mml:msub> <mml:mi>LP</mml:mi> <mml:mn>01</mml:mn> </mml:msub> </mml:mrow> </mml:math> mode, a vortex associated with the OAM state can be seen. Similar to the single-mode case, by using periodical twisting inversion, efficient OAM generation is possible. These results indicate that by simply launching fiber’s LP mode into TB-PCF, arbitrary polarization and OAM states can be generated, leading to a novel mechanism for the manipulation of the spatial state of light.
Pituitary adenylate cyclase activating peptide receptors regulate the growth of non-small cell lung cancer cells. (1995)

We have identified pituitary adenylate cyclase activating peptide (PACAP) receptors on small cell lung cancer cell line NCI-N417 in a previous study. In this study, the role of PACAP in the growth and signal transduction of non-small cell lung cancer cells was investigated. Northern blot analysis with a full-length human PACAP receptor cDNA probe revealed a major 7.5-kb hybridizing transcript when total RNA extracted from NCI-H838 cells was used. PACAP bound with high affinity (Kd = 1 nM) to a single class of sites (Bmax = 14,000/cell) when NCI-H838 cells were used. Specific 125I-labeled PACAP binding was inhibited with high affinity by PACAP-27 and PACAP-38, with moderate affinity by PACAP(6-38), and with low affinity by vasoactive intestinal polypeptide, PACAP(28-38), and PACAP(16-38). PACAP-27 elevated cAMP in a dose-dependent manner, and the increase in cAMP caused by PACAP was reversed by PACAP(6-38). PACAP-27, but not vasoactive intestinal polypeptide, elevated cytosolic Ca2+ in individual NCI-H838 cells. PACAP-27 stimulated arachidonic acid release, and the increase caused by PACAP was reversed by PACAP(6-38). PACAP-27 stimulated colony formation in NCI-H838 cells, whereas the PACAP antagonist PACAP(6-38) reduced colony formation in the absence or presence of exogenous PACAP-27. In nude mice bearing NCI-H838 xenografts, PACAP(6-38) slowed tumor growth significantly. These data suggest that biologically active type 1 PACAP receptors are present on human non-small cell lung cancer cells, which exhibit dual signal transduction pathways and regulate cell proliferation.