gebhart/patrepeval huggingface dataset:
Design and Synthesis of Novel Meta-Linked Phenylglycine Macrocyclic FVIIa Inhibitors (2016)

Two novel series of meta-linked phenylglycine-based macrocyclic FVIIa inhibitors have been designed to improve the rodent metabolic stability and PK observed with the precursor para-linked phenylglycine macrocycles. Through iterative structure-based design and optimization, the TF/FVIIa <i>K</i><sub>i</sub> was improved to subnanomolar levels with good clotting activity, metabolic stability, and permeability.
5 MUTATIONS IN K+ CHANNEL KCNJ5 (KIR3.4) COMMONLY CAUSE ALDOSTERONE-PRODUCING ADENOMAS (2012)

Aldosterone producing adenomas of the adrenal gland (APAs) are the cause of hypertension in several million people world-wide. APAs are virtually always benign and constitutively produce aldosterone despite suppression of the renin-angiotensin system. The pathogenesis of these tumors has been unknown. By exome sequencing of APAs and matched germline DNA in a discovery cohort with follow-up in a cohort of 300 APAs, we demonstrated that nearly half of these tumors have either of two somatic mutations in a K+ channel, KCNJ5. These mutations, G151R and L168R, alter the highly conserved selectivity filter of the channel. Electrophysiologic studies show that these mutations allow channels to conduct Na+ rather than just K+. This effect explains disease pathogenesis: Quiescent glomerulosa cells have a hyperpolarized membrane potential. Depolarization via angiotensin II signaling or hyperkalemia activates voltage gated Ca2+ channels; acutely, this provides the signal for aldosterone biosynthesis, while chronic elevations of intracellular Ca2+ also provide the signal for cell proliferation. Na+ influx via mutant KCNJ5 channels causes chronic membrane depolarization, accounting for both constitutive aldosterone production and cell proliferation. Proof that these mutations are sufficient to produce APAs comes from rare families with inherited germline G151R mutations in KCNJ5. These patients develop severe aldosteronism in the first years of life and develop massive bilateral adrenal hyperplasia because case every glomerulosa cell has the mutation and is proliferating and producing aldosterone. These findings provide fundamental insight into the pathogenesis of APAs and have implications for their diagnosis and treatment.
Wavelength control in fabrication of wafer fused VCSELs emitting in the 1310 nm waveband (2014)

Emission wavelength setting of 1310nm-waveband VCSELs designed for coarse wavelength division multiplexing (CWDM) 4x10 Gbps fiber-optics transmission can be controlled thanks to the wafer fusion fabrication approach. This approach allows performing the cavity adjustment before bonding the distributed Bragg reflectors (DBRs) to the active cavity of the device. Cavity adjustment was performed by digital etching with nanometer precision and proves to be very effective in compensating for epitaxial growth thickness off-set relative to nominal design and thickness nonuniformity across the wafer. With this fabrication approach we reach on fused VCSEL wafers more than 90% yield of devices that fit the CWDM wavelength slots.
Geometric and electronic structure of the Cs-doped Bi2Se3(0001) surface (2017)

Using surface x-ray diffraction and scanning tunneling microscopy in combination with first-principles calculations, we have studied the geometric and electronic structure of Cs-deposited ${\mathrm{Bi}}_{2}{\mathrm{Se}}_{3}$(0001) surface kept at room temperature. Two samples were investigated: a single ${\mathrm{Bi}}_{2}{\mathrm{Se}}_{3}$ crystal, whose surface was Ar sputtered and then annealed at $\ensuremath{\sim}500{\phantom{\rule{0.16em}{0ex}}}^{\ensuremath{\circ}}\mathrm{C}$ for several minutes prior to Cs deposition, and a 13-nm-thick epitaxial ${\mathrm{Bi}}_{2}{\mathrm{Se}}_{3}$ film that was not subject to sputtering and was annealed only at $\ensuremath{\sim}350{\phantom{\rule{0.16em}{0ex}}}^{\ensuremath{\circ}}\mathrm{C}$. In the first case, a considerable fraction of Cs atoms occupy top layer Se atoms sites both on the terraces and along the upper step edges where they form one-dimensional-like structures parallel to the step. In the second case, Cs atoms occupy the $fcc$ hollow site positions. First-principles calculations reveal that Cs atoms prefer to occupy Se positions on the ${\mathrm{Bi}}_{2}{\mathrm{Se}}_{3}$(0001) surface only if vacancies are present, which might be created during the crystal growth or during the surface preparation process. Otherwise, Cs atoms prefer to be located in $fcc$ hollow sites in agreement with the experimental finding for the MBE-grown sample.
Assignment of molecular properties of a superactive coagulation factor VIIa variant to individual amino acid changes (2002)

The most active factor VIIa (FVIIa) variants identified to date carry concurrent substitutions at positions 158, 296 and 298 with the intention of generating a thrombin-mimicking motif, optionally combined with additional replacements within the protease domain [Persson, E., Kjalke, M. & Olsen, O. H. (2001) Proc. Natl Acad. Sci. USA98, 13583-13588]. Here we have characterized variants of FVIIa mutated at one or two of these positions to assess the relative importance of the individual replacements. The E296V and M298Q mutations gave an increased intrinsic amidolytic activity (about two- and 3.5-fold, respectively) compared with wild-type FVIIa. An additive effect was observed upon their combination, resulting in the amidolytic activity of E296V/M298Q-FVIIa being close to that of the triple mutant. The level of amidolytic activity of a variant was correlated with the rate of inhibition by antithrombin (AT). Compared with wild-type FVIIa, the Ca2+ dependence of the intrinsic amidolytic activity was significantly attenuated upon introduction of the E296V mutation, but the effect was most pronounced in the triple mutant. Enhancement of the proteolytic activity requires substitution of Gln for Met298. The simultaneous presence of the V158D, E296V and M298Q mutations gives the highest intrinsic activity and is essential to achieve a dramatically higher relative increase in the proteolytic activity than that in the amidolytic activity. The N-terminal Ile153 is most efficiently buried in V158D/E296V/M298Q-FVIIa, but is less available for chemical modification also in the presence of the E296V or M298Q mutation alone. In summary, E296V and M298Q enhance the amidolytic activity and facilitate salt bridge formation between the N-terminus and Asp343, E296V reduces the Ca2+ dependence, M298Q is required for increased factor X (FX) activation, and the simultaneous presence of the V158D, E296V and M298Q mutations gives the most profound effect on all these parameters.
Alternative catalyst and exhaust gas sensor work at Argonne National Laboratory (1994)

Research programs at Argonne National Laboratory in the areas of automobile emissions monitoring and control are described. The mandate to improve automobile efficiency while reducing Pollution requires the development of new catalysts for exhaust emissions control that are capable of functioning efficiently under lean-burn engine operating conditions. It is also desirable that the use of expensive noble metal catalysts be avoided. NO{sub x} emissions will not be efficiently controlled by the current three-way, supported noble metal catalysts under lean-burn conditions. New catalysts are being sought that could effect the selective catalytic reduction (SCR) of NO{sub x} by exhaust hydrocarbons in the presence of oxygen. Molecular sieve zeolites of the ZSM-5 and ferrierite types, ion-exchanged with copper ions, are the best of the catalysts known to effect this chemistry, but the mechanism of the SCR is still not understood. In this project the authors will first undertake the investigation of the SCR of NO using model reactions to test postulated mechanistic pathways. Initial experiments have been devised to investigate the possible participation of metal alkyl complexes, metal oxime complexes, N-alkyl-N-nitroso-alkylaminato-metal complexes, and metal nitrile complexes in the zeolites. ANL will also develop microsensors, based on surface acoustic wave (SAW) chemical sensing techniques, and a micro mass-spectrometer (MS) for tailpipe or engine-out emission monitoring. The sensor configurations and sensing techniques of the proposed SAW and micro-MS are described.
Neutralizing human monoclonal antibodies prevent Zika virus infection in macaques (2017)

Therapies to prevent maternal Zika virus (ZIKV) infection and its subsequent fetal developmental complications are urgently required. We isolated three potent ZIKV-neutralizing monoclonal antibodies (nmAbs) from the plasmablasts of a ZIKV-infected patient-SMZAb1, SMZAb2, and SMZAb5-directed against two different domains of the virus. We engineered these nmAbs with Fc LALA mutations that abrogate Fcγ receptor binding, thus eliminating potential therapy-mediated antibody-dependent enhancement. We administered a cocktail of these three nmAbs to nonhuman primates 1 day before challenge with ZIKV and demonstrated that the nmAbs completely prevented viremia in serum after challenge. Given that numerous antibodies have exceptional safety profiles in humans, the cocktail described here could be rapidly developed to protect uninfected pregnant women and their fetuses.
Manufacturing implementation of IMLTMtechnology for 45nm node contact masks (2006)

For advance semiconductor manufacturing, patterning contact and via mask layers continue to be major challenge. As a result, RET's beyond the current standard 6% attPSM technology are being pursued with a goal of reducing the k 1 for hole patterning to the range of 0.35 - 0.40. IML Technology has shown promising results as a possible solution which employs strong off axis illumination (OAI) to achieve the resolution for the dense pitch contacts and the use of sub-resolution scattering bars (SB) for the semi dense to isolated contacts. At the 45nm node, placing SB by simply applying a set of rules is not sufficient for deriving the correct assist feature placements for the entire range of pitches and for the complex, randomly placed contacts that occur in actual device patterns. IML Technology utilizes modeling to locate where SB should be placed and in the case of high transmission ternary PSM (HTPSM) and CPL, defines the phase of the SB relative to the contacts being imaged. To generate such reticle designs, highly complex interference maps are calculated and from this optical interference behavior, the reticle pattern is derived. Previously, the reticle pattern derived in such a manner was extremely complex raising a question as to how feasible such an approach would be in a manufacturing environment. New algorithms which simplify the mask pattern while maintaining the resolution enhancement capability of IML have been developed. 

The objective of this work is to demonstrate a manufacturing methodology that utilizes IML Technology and is capable of meeting the requirements for the 45nm node designs. We will explore the application of this method 6% attPSM and CPL reticle designs which containing contact patterns that are representative of production devices. To define the SB for what are effectively randomly placed contacts over a wide range of pitches from dense to isolated, IML Technology is used. This modeling algorithm is based on mapping out the interference that occurs at the image plane as a result of the proximity effects of the target contact pattern. This technique provides a model-based approach for placing all types of assist features on both clear field and dark field patterns for the purpose of enhancing the printing resolution of the target pattern and it can be applied to any reticle type including binary, attPSM, altPSM, ternary HTPSM, and CPL. By implementing newly developed algorithms, simplified reticle patterns are generated which maintain the optimum SB placements determined by the IML process.
Supplementary Figure 1 from HER2 Isoforms Uniquely Program Intratumor Heterogeneity and Predetermine Breast Cancer Trajectories During the Occult Tumorigenic Phase (2023)

&lt;p&gt;HER2BOW transgene design&lt;/p&gt;
Deployable micro-traps to sequester motile bacteria (2017)

The development of strategies to reduce the load of unwanted bacteria is a fundamental challenge in industrial processing, environmental sciences and medical applications. Here, we report a new method to sequester motile bacteria from a liquid, based on passive, deployable micro-traps that confine bacteria using micro-funnels that open into trapping chambers. Even in low concentrations, micro-traps afford a 70% reduction in the amount of bacteria in a liquid sample, with a potential to reach >90% as shown by modelling improved geometries. This work introduces a new approach to contain the growth of bacteria without chemical means, an advantage of particular importance given the alarming growth of pan-drug-resistant bacteria.
Interoperable CFP-DCO and CFP2-DCO Pluggable Optic Interfaces for 100G WDM Transmission (2019)

For the first time, interoperability is demonstrated at 100G with modern CFP-DCO and CFP2-DCO interfaces using the newly standardized Staircase FEC between three vendors and two DSP-ASIC providers. Inter-workable 100G WDM transmission (up to 1200 km) and passive point-to-point interconnection (up to 135 km) are shown.
Supplementary Figures 1 - 7 from Effective Delivery of a Microtubule Polymerization Inhibitor Synergizes with Standard Regimens in Models of Pancreatic Ductal Adenocarcinoma (2023)

&lt;p&gt;Supplementary Figures 1 - 7&lt;/p&gt;
Pen pressure control in trajectory-based interaction (2009)

This study presents a series of three experiments that evaluate human capabilities and limitations in using pen-tip pressure as an additional channel of control information in carrying out trajectory tasks such as drawing, writing and gesturing on computer screen. The first experiment measured the natural range of force used in regular drawing and writing tasks. The second experiment tested human performance of maintaining pen-tip pressure at different levels with and without a visual display of the pen pressure. The third experiment, using the steering law paradigm, studied path steering performance as a function of the steering law index of difficulty, steering path type (linear and circular) and pressure precision tolerance interval. The main conclusions of our investigation are as follows. The natural range of pressure used in drawing and writing is concentrated in the 0.82 N (SI force unit Newton (N) is used in this article) to 3.16 N region. The resting force of the pen tip on the screen is between 0.78 N and 1.58 N. Pressure near or below the resting force is markedly more difficult to control. Visual feedback improves pressure-modulated trajectory tasks. Up to six layers of pressure can be controlled in steering tasks, but the error rate changed from 4.9% for one layer of pressure to 35% for six layers. The steering law holds for pressure steering tasks, which enables systematic prediction of successful steering time for a given path's length, width and pressure precision criterion. The steering time can also be modelled as a logarithmic function of pressure control precision ratio σ. Taken together, the current work provides a systematic body of empirical knowledge as basis for future research and design of digital pen applications.
692. A Novel RNAi Trigger Design Retains Potent, Target Specific Activity Despite Emerging Mutations in the Target Site (2015)

Conventional si/shRNA designs are restricted to Watson/Crick pairing between guide strand and target RNA as this has been deemed crucial for potent Argonaute 2 based slicer activity. Despite individual publications partially challenging the requirement of sole Watson/Crick pairing these results have not yet found entry into RNAi designs. By rational incorporation of results from RNA crystallography structures and non-canonical and non-Watson/Crick pairings (nWCp) at certain positions we have developed a novel RNAi trigger design. Our approach allowed us to create shRNAs where a single guide strand suppresses a spectrum of target sequences through Argonaute 2 activity with target specificity, and similar or higher potency than a conventional design. Genomic off target effects were not observed in NGS analysis. In target/guide variant analysis several guide strands demonstrated potent RNAi activity even with G/U pairings at numerous positions or G/G pairings at position 10 or 11. Furthermore we demonstrate that this approach allows the application of RNAi against mutating targets as verified against HIV-1. Thus, our results demonstrate that an RNAi trigger can be applied to any therapeutic target (with an accessible RNA) prone to mutation-based resistance/escape offering significant improvement to the therapeutics of both infectious diseases and cancer. Additionally, we provide evidence that target and off-target prediction rules for microRNAs and shRNA/siRNAs may benefit from revisions to include a significantly wider set of pairings.
Passively temperature-compensated fibre Fabry–Perot filter and its application in wavelength division multiple access computer network (1990)

Tunable fibre Fabry–Perot filters were constructed and tested to meet the optical and mechanical requirements for a direct detection, passive optical wavelength division multiple access (WDMA) computer network to interconnect computer work stations.
Design of novel loss functions for deep learning in x-ray CT (2022)

Deep learning (DL) shows promise of advantages over conventional signal processing techniques in a variety of imaging applications. The networks’ being trained from examples of data rather than explicitly designed allows them to learn signal and noise characteristics to most effectively construct a mapping from corrupted data to higher quality representations. In inverse problems, one has options of applying DL in the domain of the originally captured data, in the transformed domain of the desired final representation, or both. X-ray computed tomography (CT), one of the most valuable tools in medical diagnostics, is already being improved by DL methods. Whether for removal of common quantum noise resulting from the Poisson-distributed photon counts, or for reduction of the ill effects of metal implants on image quality, researchers have begun employing DL widely in CT. The selection of training data is driven quite directly by the corruption on which the focus lies. However, the way in which differences between the target signal and measured data is penalized in training generally follows conventional, pointwise loss functions. This work introduces a creative technique for favoring reconstruction characteristics that are not well described by norms such as mean-squared or mean-absolute error. Particularly in a field such as X-ray CT, where radiologists’ subjective preferences in image characteristics are key to acceptance, it may be desirable to penalize differences in DL more creatively. This penalty may be applied in the data domain, here the CT sinogram, or in the reconstructed image. We design loss functions for both shaping and selectively preserving frequency content of the signal.
A new approach of light microscopic immunohistochemical triple-staining: combination of Fos labeling with diaminobenzidine-nickel and neuropeptides labeled with Alexa488 and Alexa555 fluorescent dyes (2012)

Alexa488 and Alexa555 fluorescent dyes, Fos, hypocretin, melanin-concentrating hormone, cryostat sections, triple labeling immunohistochemistry, rat.
A pivot-based index structure for combination of feature vectors (2005)

We present a novel indexing schema that provides efficient nearest-neighbor queries in multimedia databases consisting of objects described by multiple feature vectors. The benefits of the simultaneous usage of several (statically or dynamically) weighted feature vectors with respect to retrieval effectiveness have been previously demonstrated. Support for efficient multi-feature vector similarity queries is an open problem, as existing indexing methods do not support dynamically parameterized distance functions. We present a solution for this problem relying on a combination of several pivot-based metric indices. We define the index structure, present algorithms for performing nearest-neighbor queries on these structures, and demonstrate the feasibility by experiments conducted on two real-world image databases. The experimental results show a significant performance improvement over existing access methods.
Neutralization of interleukin-18 reduces severity in murine colitis and intestinal IFN-γ and TNF-α production (2001)

Interleukin (IL)-18, initially described as interferon (IFN)-gamma-inducing factor, is expressed in the inflamed mucosa of patients with Crohn's disease. To investigate the role of IL-18 in intestinal inflammation, the effect of neutralizing antimurine IL-18 antiserum in dextran sulfate sodium (DSS)-induced colitis in BALB/c and C57BL/6 mice was examined. During a dose response of DSS, levels of colonic IL-18 increased parallel with clinical worsening. With the use of confocal laser microscopy, the increased IL-18 was localized to the intestinal epithelial layer. Anti-IL-18 treatment resulted in a dose-dependent reduction of the severity of colitis in both BALB/c and C57BL/6 mice. Colon shortening following DSS-induced colitis was partially prevented in the treatment groups. In the colon tissue homogenates, IFN-gamma concentrations were lower in the anti-IL-18-treated DSS-fed mice compared with untreated DSS-fed mice. This suppressive effect of anti-IL-18 administered in vivo was also observed on spontaneous tumor necrosis factor-alpha, IL-18, and IFN-gamma production from ex vivo colon organ cultures. The stimulation of lamina propria mononuclear cells by IL-18 and IL-12 resulted in a synergistic increase in IFN-gamma synthesis. These findings suggest that IL-18 is a pivotal mediator in experimental colitis.
Performance of infra-plant overtime policies (1995)

Abstract Production quotas smooth production in order to synchronize inter-plant production networks. To meet quotas, plants work overtime whenever they're behind. In addition to this 'mandatory' overtime required to satisfy the quota of finished product at the end of the line, many plants run selected stations within the plant overtime to fill critical buffers within the plant. We call this intra-plant overtime 'preventive' overtime because by spending a little overtime this shift on critical stations, the plant can avoid massive overtime next shift. We describe this real production control problem currently facing industry. The problem arises because of (often underestimated or ignored) production variability. We exhibit actual production data that shows the degree of variability often inherent in current manufacturing processes. We describe four policies and compare them using simulation.