gebhart/patrepeval huggingface dataset:
Pyrogenic, Lethal, and Emetic Properties of Superantigens in Rabbits and Primates (2003)

Superantigens (SAgs) stimulate large fractions of T cells by circumventing normal antigen presentation through binding both class II major histocompatibility complex (MHC) molecules on antigen-presenting cells, and specific variable regions on the β-chain (Vβ) of the T-cell antigen receptor (TCR) (1,2). The bacterial SAgs produced from coagulase positive staphylococci (Staphylococcus aureus) and group A streptococci (GAS; Streptococcus pyogenes) belong to the large and expanding family of pyrogenic toxins, and various members of this group of SAgs have a clear involvement in the toxic shock syndrome (TSS). Through SAg-mediated stimulation, Tlymphocytes are activated at several orders of magnitude above antigen-specific activation, resulting in the extensive release of cytokines that are believed to be responsible for the most severe features of TSS. SAgs from S. aureus include toxic shock syndrome toxin-1 (TSST-1), multiple staphylococcal enterotoxin (SE) serotypes (A through P, excluding F), while SAgs from S. pyogenes include streptococcal pyrogenic exotoxin (SPE) serotypes (A, C, G, H, I, J) as well as streptococcal superantigen (SSA) and multiple streptococcal mitogenic exotoxin Z (SMEZ) variants (3-5). The toxins within this class of SAgs that have been tested are all pyrogenic, and all are likely to be capable to induce TSS in susceptible hosts if supplied in sufficient quantity.
VAMP2 AND SYNAPTOTAGMINS ARE RELATIVELY IMMOBILE ON CHROMAFFIN GRANULE MEMBRANES: IMPLICATIONS FOR MEMBRANE FUSION AND FUSION PORE EXPANSION (2021)

Abstract Although many of the proteins of secretory granules have been identified, little is known about their molecular organization and diffusion characteristics. Granule-plasma membrane fusion can only occur when proteins that enable fusion are present at the granule-plasma membrane contact. Thus, the mobility of granule membrane proteins may be an important determinant of fusion pore formation and expansion. To address this issue, we measured the mobility of (fluorophore-tagged) vesicle associated membrane protein 2 (VAMP2), synaptotagmin 1 (Syt1), and synaptotagmin 7 (Syt7) in chromaffin granule membranes in living chromaffin cells. We used a method that is not limited by standard optical resolution. A bright flash of strongly decaying evanescent field (∼80 nm exponential decay constant) produced by total internal reflection (TIR) was used to photobleach GFP-labeled proteins in the granule membrane. Fluorescence recovery occurs as unbleached protein in the granule membrane distal from the glass interface diffuses into the more bleached proximal regions, thereby enabling the measurement of diffusion coefficients. The studies revealed that VAMP2, Syt1, and Syt7 are relatively immobile in chromaffin granules membranes with diffusion constants of ≤ 3 × 10 −10 cm 2 /s. Utilizing these diffusion parameters and the known density of VAMP2 and Syt 1 on synaptic vesicles, we estimated the time required for these proteins to arrive at a nascent fusion site to be tens of milliseconds. We propose that the mobilities of secretory granule SNARE and Syt proteins, heretofore unappreciated factors, influence the kinetics of exocytosis and protein discharge. Significance Statement In eukaryotic cells, secretory vesicles fuse with the plasma membrane to secrete chemical transmitters, hormones and proteins that enable diverse physiological functions including neurotransmission. Fusion proteins need to be assembled at the fusion site in sufficient number in order to enable membrane fusion. However, the diffusion characteristics of fusogenic proteins on secretory vesicles remained unknown. Here we used a novel method not limited by standard optical resolution to measure the diffusion of VAMP2 and synaptotagmins on chromaffin granule membranes. We found they have limited mobility. The time required for these proteins to reach the granule-plasma membrane contact site suggests that their limited mobility likely influences the kinetics of membrane fusion and subsequent fusion pore expansion.
Biosynthetic Gene Cluster of Linaridin Peptides Contains Epimerase Gene (2022)

Salinipeptins belong to the type-A linaridin class of ribosomally synthesized and post-translationally modified peptides (RiPPs) comprising 22 amino acid residues with multiple D-amino acids. Although chirality of other type-A linaridins, such as grisemycin and cypemycin, has not been reported, the biosynthetic gene clusters of type-A linaridins have identical gene organization. Here, we report heterologous expression of grisemycin biosynthetic gene cluster (grm) and show that grisemycin contains multiple D-amino acids, similar to salinipeptins. The heterologous expression experiments also confirm the involvement of a novel peptide epimerase in grisemycin biosynthesis. Gene-deletion experiments indicate that grmL, a single gene with unknown function, is indispensable for grisemycin production. We also show that the presence of D-amino acids is likely a common feature of linaridin natural products by analyzing two other type-A linaridin clusters.
Participation of a Stress‐Activated Protein Kinase Cascade in the Activation of Tyrosine Hydroxylase in Chromaffin Cells (1997)

Sodium arsenite and osmotic shock both stimulated stress-activated protein kinase-2 (SAPK2, also termed RK, p38, CSBP and Mxi2) and its downstream target mitogen-activated protein kinase (MAP kinase)-activated protein kinase-2 (MAPKAP-K2) in bovine adrenal chromaffin and rat PC12 cells. The same stimuli also increased tyrosine hydroxylase activity 2-3-fold and induced its phosphorylation at Ser19, a residue phosphorylated by MAPKAP-K2 in vitro. The arsenite-induced activation of tyrosine hydroxylase and its phosphorylation at Ser19 were prevented by SB 203580 at concentrations similar to those that inhibited SAPK2 in vitro. These results indicate that MAPKAP-K2 mediates the stress-induced activation of tyrosine hydroxylase. SB 203580 had no effect on the phosphorylation or activation of tyrosine hydroxylase induced by nerve growth factor or forskolin, which trigger the phosphorylation of Ser31 and Ser40, respectively. Stimulation of bovine adrenal chromaffin cells with acetylcholine activated SAPK2 and MAPKAP-K2, as well as p42/p44 MAP kinases and their downstream target MAPKAP-K1. The half-times for activation of MAPKAP-K1 and MAPKAP-K2 (1 min) were similar. In contrast, the activation of tyrosine hydroxylase by acetylcholine peaked within 1 min and gradually declined thereafter. Neither SB 203580 (which blocked the activation of MAPKAP-K2 by acetylcholine) nor PD 98059 (which prevented the activation of p42/p44 MAP kinases by acetylcholine) affected tyrosine hydroxylase activation after 1 min, but these compounds inhibited activation by 40-50% after 5 min. PD 98059 prevented the acetylcholine-induced phosphorylation of tyrosine hydroxylase at Ser31, the residue targetted by p42/p44 MAP kinases in vitro, but did not inhibit the phosphorylation of Ser40 (which is phosphorylated by MAPKAP-K1 in vitro). Our results establish that p42/p44 MAP kinases mediate the acetylcholine-induced phosphorylation of tyrosine hydroxylase at Ser31. SB 203580 did not suppress the phosphorylation of Ser19 or Ser40 by acetylcholine but, like PD 98059, this drug decreased the phosphorylation of Ser31. SAPK2 may therefore contribute to the acetylcholine-induced activation of tyrosine hydroxylase by facilitating (in an unknown way) its phosphorylation by MAP kinases.
Is There an Association Between the “Critical Shoulder Angle” and Clinical Outcome after Rotator Cuff Repair? (2016)

Objectives: Variations in scapular morphology have been associated with the development of atraumatic rotator cuff tears (RCT). Current theories suggest a morphologic predisposition for altered shoulder biomechanics favoring the development of RCTs. The critical shoulder angle (CSA) is a radiographic measure that accounts for both glenoid inclination and lateral extension of the acromion, and angles &gt;35 degrees are reported to be correlated with the development of degenerative RCTs. The impact of the CSA on outcomes following rotator cuff repair (RCR) has not previously been investigated. The purpose of this study was to investigate the relationship between the CSA and clinical outcomes after rotator cuff repair. Methods: As part of a prospective observational cohort study we obtained CSA measurements for 144 patients with documented full-thickness RCTs who were followed up for a minimum of 48 weeks. Patients were then stratified based on RCT etiology and treatment. Demographic data as well as The Western Ontario Rotator Cuff Index (WORC), American Shoulder and Elbow Surgeons (ASES) score and Visual Analog Scale (VAS) for pain were collected at baseline, four, eight, 16, 32 and 48 weeks. The CSA for all of the patients was measured retrospectively, with all assessors being blinded to the data and we calculated interclass correlation coefficients (ICC) to measure agreement. The statistical analysis included longitudinal multilevel regression modeling to investigate the association of the CSA and the WORC, ASES and VAS for pain. Results: Controlling for demographic and clinical characteristics, patients with CSAs less than 38 degrees reported better outcome scores over time compared to those with CSAs greater than 38 degrees (WORC: B=-106.6, p=0.025, ASES: B=4.83, p=0.0001, VAS: B=-12.99, p=0.0001). Interobserver and intraobserver reliability for CSA measurements resulted in an ICC of 0.969 and 0.982 respectively, indicating excellent agreement. Conclusion: We found that a CSA less than 38 degrees was associated with better outcomes in patients following surgical repair of atraumatic full-thickness rotator cuff tears. This is the first study to examine the relationship between the CSA and outcomes following RCR. These findings suggest that individual scapular morphology may influence both disease development and surgical outcomes of rotator cuff tears. This association warrants further investigation.
Reversible inhibition of cholinesterases with aromatic N-substituted 2-hydroxyiminoacetamides (2014)

Acetylcholinesterase (AChE ; EC 3.1.1.7) and butyrylcholinesterase (BChE ; EC 3.1.1.8) are class of hydrolases that play important role in neurotransmission and biotransformation of xenobiotics. Organophosphorus (OP) nerve agents acting as an irreversible AChE inhibitors represent a persistent threat to general population as a consequence of their use as warfare agents in armed conflicts and terrorist attacks or as pest control agents. Thus, current therapy in case of OP nerve agent poisoning includes reactivation of AChE by quaternary pyridinuim oximes. However, due to their permanent positive charge, these compounds do not readily cross the blood-brain barrier and thus cannot reactivate AChE in central nervous system. We evaluated affinity of AChE and BChE for novel class of centrally acting reactivators derived from previously reported N-substituted 2-hydroxyiminoacetamide scaffold. We introduced a phenyl ring in the structure of N-substituted 2-hydroxyiminoacetames using cinnamyl alcohol as starting compound. 1-phenyl-allylamine was prepared from cinnamyl alcohol in Overman reaction and an azide group was introduced via a three-step process. An azide group has enabled us to prepare more elaborate structures by the well-known copper catalysed azide-alkyne cycloaddition. Novel aromatic N-substituted 2-hydroxyiminoacetamides differ in their AChE peripheral site binding moiety ranging from an azide group to functionalized heterocycles connected with central N-(1-phenylpropyl)-2-hydroxyiminoacetamide scaffold via 1, 2, 3-triazole ring. Structural diversity of new compounds allowed us to determine the importance of ligand peripheral site binding properties for the overall stabilization and binding affinity. Molecular docking studies were performed on all new compounds to help us rationalize observed differences between their binding affinities. Difference in AChE/BChE affinity will indicate whether new compounds are selective ligands of AChE or can be further developed as general type of ligands for both AChE and BChE. These compounds lack a permanent positive charge and, therefore, it is expected for them to cross the blood-brain barrier with greater capacity than quaternary pyridinuim oximes in use.
Honey protects against cisplatin-induced hepatic and renal toxicity through inhibition of NF-κB-mediated COX-2 expression and the oxidative stress dependent BAX/Bcl-2/caspase-3 apoptotic pathway (2018)

The protective effects of both manuka and talh honeys were assessed using a rat model of cisplatin (CISP)-induced hepatotoxicity and nephrotoxicity. The results revealed that both honeys exerted a protective effect against CISP-induced hepatotoxicity and nephrotoxicity as demonstrated by decreasing liver and kidney function. Manuka honey also prevented CISP-induced histopathological changes observed in the liver and decreased the changes seen in the kidneys. Talh honey decreased CISP-induced liver histopathological changes but had no effect on CISP-induced kidney histopathological changes. Both honeys reduced the oxidative stress in the liver. Conversely, they have no effect on kidney oxidative stress, except that manuka honey increased CAT activity. GC-MS analysis showed the presence of the antioxidant octadecanoic acid in talh honey while heneicosane and hydrocinnamic acid were present at a higher content in manuka honey. The molecular mechanism was to limit the expression of inflammatory signals, including COX-2 and NF-κB, and the expression of the apoptotic signal, BAX and caspase-3 while inducing Bcl-2 expression.
Silicon-based products and solutions (2014)

TeraXion started silicon photonics activities aiming at developing building blocks for new products and customized solutions. Passive and active devices have been developed including MMI couplers, power splitters, Bragg grating filters, high responsivity photodetectors, high speed modulators and variable optical attenuators. Packaging solutions including fiber attachment and hybrid integration using flip-chip were also developed. More specifically, a compact packaged integrated coherent receiver has been realized. Good performances were obtained as demonstrated by our system tests results showing transmission up to 4800 km with BER below hard FEC threshold. The package size is small but still limited by the electrical interface. Migrating to more compact RF interface would allow realizing the full benefit of this technology.
WE‐E‐103‐02: Past, Present and Future Roles of ROC Analysis in Medical Imaging and Quantitative Image Analysis (2013)

Receiver Operating Characteristic (ROC) analysis has been a mainstay of many research developments as well as various clinical studies/trials. It has provided medical physicists with a way to objectively measure how data are presented in an image, how people perceive those images, and how one can compare different observers or different imaging modalities with each other. ROC analysis plays an important role in both technology assessment and clinical decision‐making, especially as various aspects of imaging biomarkers and personalized medicine are evaluated. Over the past five years, on average, almost 40 papers/year that were published in MEDICAL PHYSICS utilized ROC analysis. The challenges and opportunities in ROC analysis research and in its application in various tasks are active areas, including expanding the mathematical formulation for multiple lesions per image, location‐based sensitivity, and evaluation without ground truth, as well as expanding its role in imaging biomarker validation, assessing response to therapy, theranostics, and image‐based phenotyping with genomics (image‐omics). Learning Objectives: 1. Review the mathematical foundations and implementation of ROC analysis in basic research and clinical trials; and understand the role and limitations of ROC analysis in large scale clinical studies/trials 2. Recognize advances in ROC analysis in order to incorporate multiple lesions per image, location‐based sensitivity, evaluation without ground truth, theranostics, and others 3. Appreciate the evolving role of ROC analysis in the evaluation of imaging biomarkers and image‐based phenotyping Research supported by NIH, DOE, and DOD. COI: Stockholder, Hologic, Inc Shareholder, Quantitative Insights, Inc Royalties, Hologic, Inc Royalties, General Electric Company Royalties, MEDIAN Technologies Royalties, Riverain Technologies, LLC Royalties, Mitsubishi Corporation Royalties, Toshiba Maryellen Giger Corporation Researcher, Koninklijke Philips Electronics NV Researcher, U‐Systems, Inc
Generating Certificate Requests for Short-Term, Automatically-Renewed (STAR) Certificates (2018)

This memo proposes a protocol that allows a domain name owner to
delegate to a third party (such as a CDN) control over a certificate
that bears one or more names in that domain. Specifically the third
party creates a Certificate Signing Request for the domain, which can
then be used by the domain owner to request a short term and
automatically renewed (STAR) certificate. This is a component in a
solution where a third-party such as a CDN can terminate TLS sessions
on behalf of a domain name owner (e.g., a content provider), and the
domain owner can cancel this delegation at any time without having to
rely on certificate revocation mechanisms.
Supplementary Table 1 from NOTCH Is Part of the Transcriptional Network Regulating Cell Growth and Survival in Mouse Plasmacytomas (2023)

Supplementary Table 1 from NOTCH Is Part of the Transcriptional Network Regulating Cell Growth and Survival in Mouse Plasmacytomas
An efficient blind modulation detection for adaptive OFDM systems (2003)

Adaptive modulation is a method to increase the data capacity, throughput and efficiency of time division duplexed wireless communication systems. In adaptive modulation, the transmitter continually monitors the dynamic channel and adjusts the transmission parameters such as modulation order, coding rate etc. accordingly. Blind modulation detection schemes play an important role in adaptive systems to eliminate the need for transmitting modulation information, thereby increasing spectral efficiency. In this paper, an improved statistical blind modulation detection method based on the Kullback-Leibler distance is proposed for OFDM based wireless communication systems. Simulation results show that this blind modulation detection algorithm outperforms similar previously proposed algorithms.
Improving robustness of cyclostationary detectors to cyclic frequency mismatch using Slepian basis (2015)

Spectrum Sensing (SS) is one of the fundamental mechanisms required by a Cognitive Radio (CR). Among several SS techniques, cyclostationary feature detection is considered as an important technique due to its robustness against noise variance uncertainty and its capability to distinguish among different systems on the basis of their cyclostationary features. However, one of the main limitations of this detector in practical scenarios is its performance degradation in the presence of cyclic frequency mismatch, which mainly arises due to the lack of knowledge about the transmitter clock/oscillator errors at the detector. In this context, this paper proposes a novel solution to address the cyclic frequency mismatch problem utilizing the Slepian basis expansion instead of the widely used Fourier basis expansion. It is shown that the proposed approach captures the deviation in the cyclic frequency caused by the aforementioned imperfections and hence provides a significant improvement in the sensing performance in the presence of cyclic frequency mismatch.
Quantitative Assessment of Promoter Methylation Profiles in Thyroid Neoplasms (2005)

Methylation-induced gene silencing appears to affect multiple genes in thyroid tissue and increases with cancer progression. Additional markers with better discriminatory power between benign and malignant samples are needed for the diagnostic assessment of cytologically indeterminate thyroid nodules.
Model-based passivity control for bilateral teleoperation of a surgical robot with time delay (2008)

In minimally invasive telesurgical systems, displaying the forces measured at the slave side is an important issue. Latency in communication lines limits the transmission of vivid tactile sensations and drives the system unstable. In this paper, we propose a new model-based approach for the bilateral control of a telesurgical robot using time-domain passivity control. This method consists of a virtual slave model implemented at the master side to estimate the force on the slave side. During the operation, the estimated force from the virtual slave is added to the actual measured force transmitted from the slave in order to maintain the passivity of the system. Both simulation and experimental results confirm the performance of this new controller.
Effects of Plasma-Induced Si Recess Structure on n-MOSFET Performance Degradation (2009)

Performance degradation of n-MOSFETs with plasma-induced recess structure was investigated. The depth of Si recess (dR) was estimated from the experiments by using Ar gas plasmas. We propose an analytical model by assuming that the damage layer was formed during an offset spacer etch. A linear relationship between threshold voltage shift (DeltaV <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> ) and <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">d</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R</sub> was found. Device simulations were also performed for n-MOSFETs with various (d <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R</sub> ). Both |DeltaV <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> | and off-state leakage current increased with an increase in <i xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">d</i> <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R</sub> . The increase in |DeltaV <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> | becomes larger for smaller gate length. The results from device simulations are consistent with the analytical model. These findings imply that the Si recess structure induced by plasma damage enhances V <sub xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">th</sub> -variability in future devices.