gebhart/patrepeval huggingface dataset:
Actin-binding domain of Rng2 sparsely bound on F-actin strongly inhibits actin movement on myosin II (2022)

We report a case in which sub-stoichiometric binding of an actin-binding protein has profound structural and functional consequences, providing an insight into the fundamental properties of actin regulation. Rng2 is an IQGAP contained in contractile rings in the fission yeast <i>Schizosaccharomyces pombe</i> Here, we used high-speed atomic force microscopy and electron microscopy and found that sub-stoichiometric binding of the calponin-homology actin-binding domain of Rng2 (Rng2CHD) induces global structural changes in skeletal muscle actin filaments, including shortening of the filament helical pitch. Sub-stoichiometric binding of Rng2CHD also reduced the affinity between actin filaments and muscle myosin II carrying ADP and strongly inhibited the motility of actin filaments on myosin II in vitro. On skeletal muscle myosin II-coated surfaces, Rng2CHD stopped the actin movements at a binding ratio of 11%. Rng2CHD also inhibited actin movements on myosin II of the amoeba <i>Dictyostelium</i>, but in this case, by detaching actin filaments from myosin II-coated surfaces. Thus, sparsely bound Rng2CHD induces apparently cooperative structural changes in actin filaments and inhibits force generation by actomyosin II.
Intranucleolar sites of ribosome biogenesis defined by the localization of early binding ribosomal proteins (2007)

Considerable efforts are being undertaken to elucidate the processes of ribosome biogenesis. Although various preribosomal RNP complexes have been isolated and molecularly characterized, the order of ribosomal protein (r-protein) addition to the emerging ribosome subunits is largely unknown. Furthermore, the correlation between the ribosome assembly pathway and the structural organization of the dedicated ribosome factory, the nucleolus, is not well established. We have analyzed the nucleolar localization of several early binding r-proteins in human cells, applying various methods, including live-cell imaging and electron microscopy. We have located all examined r-proteins (S4, S6, S7, S9, S14, and L4) in the granular component (GC), which is the nucleolar region where later pre-ribosomal RNA (rRNA) processing steps take place. These results imply that early binding r-proteins do not assemble with nascent pre-rRNA transcripts in the dense fibrillar component (DFC), as is generally believed, and provide a link between r-protein assembly and the emergence of distinct granules at the DFC-GC interface.
Biofunctional Nanodot Arrays in Living Cells Uncover Synergistic Co‐Condensation of Wnt Signalodroplets (2022)

Qualitative and quantitative analysis of transient signaling platforms in the plasma membrane has remained a key experimental challenge. Here, biofunctional nanodot arrays (bNDAs) are developed to spatially control dimerization and clustering of cell surface receptors at the nanoscale. High-contrast bNDAs with spot diameters of ≈300 nm are obtained by capillary nanostamping of bovine serum albumin bioconjugates, which are subsequently biofunctionalized by reaction with tandem anti-green fluorescence protein (GFP) clamp fusions. Spatially controlled assembly of active Wnt signalosomes is achieved at the nanoscale in the plasma membrane of live cells by capturing the co-receptor Lrp6 into bNDAs via an extracellular GFP tag. Strikingly, co-recruitment is observed of co-receptor Frizzled-8 as well as the cytosolic scaffold proteins Axin-1 and Disheveled-2 into Lrp6 nanodots in the absence of ligand. Density variation and the high dynamics of effector proteins uncover highly cooperative liquid-liquid phase separation (LLPS)-driven assembly of Wnt "signalodroplets" at the plasma membrane, pinpointing the synergistic effects of LLPS for Wnt signaling amplification. These insights highlight the potential of bNDAs for systematically interrogating nanoscale signaling platforms and condensation at the plasma membrane of live cells.
Electronic/Hydraulic Level Gage (1986)

System for checking levelness of machines and structures requires less time and labor than conventional optical systems. Measures differences in elevation to within 0.002 in. (0.05 mm). Floats at opposite ends of structure determine positions of cores in linear variable-differential transformers. Outputs of LVDT's carried by cables to control console, where displayed to operator as difference in core levels and therfore of ends of structure.
Aktivierungsparameter und Stereochemie einer Antikörper‐katalysierten Claisen‐Umlagerung (1992)

Die gleiche Reaktion mit unterschiedlichen Mechanismen zu katalysieren , das gelingt dank der Diversität der Immunantwort. So sind Antikörper bekannt die die Chorismat‐Prephenat‐Umwandlung 1 ) 3 mit unterschiedlichen Aktivierungsparametern katalysieren, wobei die Antikörper jeweils gegen ein Analogon des Übergangszustands 2 erzeugt wurden. Für den Antikörper 11F1–2E11 wurde jetzt eine extrem niedrige Aktivierungsentropie gefunden, ein Hinweis darauf, daß das Konzept der „Konformationseinschränkung”︁ bei der Antikörperkatalyse zuzutreffen scheint. magnified image
Theoretical Analysis of the Effects of Cigarette Design Parameters on the Smoldering Rates, Heat Flux, and Total Heat Released during Smoldering of a Cigarette (2001)

A mathematical model developed by Muramatsu, Umemura, and Okada (1979) was modified and improved by changing the relative amounts of radiative and conductive heat transfer to study the effects of moisture content in the cigarette, cigarette packing density, and cigarette circumference on the smoldering rates, heat flux, and total heat released during natural smolder of a cigarette. A mathematically predicted temperature profile was fitted to the corresponding experimental values with a nonlinear least-square fitting routine to obtain a smoldering rate and the relative amounts of radiative and conductive heat transfer. Then, based on the relative contribution of heat transfer modes, the heat flux and the total heat released were calculated with the fitted smoldering rate as a function of cigarette design parameters. Results show that the circumference of the cigarette is the major physical factor affecting mass burn rate (MBR), while the packing density of the cigarette strongly affects the linear burn rate (LBR), heat flux, and total heat released.
Biomedical Engineering in Epidural Anaesthesia Research (2013)

The application of engineering techniques into biomedical procedures has proved extremely beneficial in many areas of medicine. A developing area is in epidural analgesia and anaesthesia, a technique employed for the relief of pain in both acute and chronic, and for anaesthesia to enable pain-free surgery. The aim of this chapter is to demonstrate several specific areas of research and how biomedical engineering techniques are used to improve and enhance the experience and training in the epidural procedure. The overall goal is to reduce the risks and subsequent morbidity in patients using advanced technologies to recreate the epidural procedure replicating as far as possible the in-vivo procedure. This would allow anaesthetists to practice the procedure in a safe and controlled environment without risk to patients. This could be achieved by recreating the sensation of the needle passing through the tissues and ligaments and by the generation of forces that match exactly those felt in-vivo. Epidural simulators are currently used as a training aid for anaesthetists, however existing simulators lack realism to various degrees and their operation is not based on measured invivo data that can accurately simulate the procedure. The techniques of advanced simulation and biomedical engineering detailed in this chapter can provide a solution.
Using Public Data for Comparative Proteome Analysis in Precision Medicine Programs (2017)

Together, these data establish the potential for state-of-the-art MS-based proteomics data to serve as resources for robust comparative analyses in precision medicine applications.
Light in AI: Toward Efficient Neurocomputing With Optical Neural Networks—A Tutorial (2022)

In the post Moore’s era, conventional electronic digital computing platforms have encountered escalating challenges to support massively parallel and energy-hungry artificial intelligence (AI) workloads. Intelligent applications in data centers, edge devices, and autonomous vehicles have restricted requirements in throughput, power, and latency, which raises a high demand for a revolutionary neurocomputing solution. Optical neural network (ONN) is a promising hardware platform that could represent a paradigm shift in efficient neurocomputing with its ultra-fast speed, high parallelism, and low energy consumption. In recent years, efforts have been made to facilitate the ONN design stack and push forward the practical application of optical neural accelerators. In this tutorial, we give an overview of state-of-the-art cross-layer co-design methodologies for scalable, robust, and self-learnable ONN designs across the circuit, architecture, and algorithm levels. Besides, we analyze challenges and highlight emerging directions targeting next-generation optics for AI.
Effect of Long-term Ingestion of Porcine Elastin Peptide on Human Skin Elasticity (2011)

ブタ大動脈を原料としてエラスチン加水分解ペプチド（エラスチンペプチド）を調製し，その摂取がヒトの皮膚弾力性にもたらす影響について検討した．はじめに，エラスチンペプチド経口摂取後のヒト血液中のアミノ酸濃度の変化を観察した．成人男性5名を被験者として，12時間絶食後にエラスチンペプチドを摂取させた．その結果，エラスチンペプチド経口摂取後に血中の総アミノ酸量が増加し，増加したアミノ酸の組成は，摂取したエラスチンペプチドのアミノ酸組成に類似していた．また，ハイドロキシプロリンおよびアルギニンがそれぞれペプチド態として血中に検出され，エラスチンペプチドの少なくとも一部はペプチド態として血中に移行していると考えられた．次に，39名の中高齢者を3群にわけ1日量0, 100, 200mgのエラスチンペプチドを8週間継続摂取させ皮膚弾力性を測定した．100mg, 200mg摂取群において摂取開始8週目に摂取前と比較して有意に皮膚弾力性が上昇した．またその変化率は0mgと比較して200mg群で有意に高値を示した．以上より，エラスチンペプチドの経口摂取はヒトの皮膚弾力性を向上させることが示唆された．
Design optimization for energy-efficient pulse-switching networks in carrier-injection based Si-photonics (2019)

We compare pulse-switching operations in MZI- and ring-switches both experimentally and based on large-signal circuit simulations. With a modification in switch design and with optimization of phase modulator lengths, we show high-speed switches with potential for an over 3 dB improvement in energy consumption.
An Analytical Approach to the Calculation of EVM in Clipped Multi-Carrier Signals (2012)

Error vector magnitude (EVM) is an important figure of merit in many communication systems. In this work an analytical approach to the calculation of EVM in clipped multi- carrier signals is proposed. In contrast to previous work, the EVM in this work is calculated with no simplifying model (e.g. a Gaussian assumption). The expression is given in a form of a power series. Based on the derived expressions for EVM, bounds on the maximal achievable rate are derived.
Abstract 2212: Cellular and molecular changes associated with lung squamous premalignant lesion severity identified by single-cell RNA-seq (2021)

Abstract Background: Sampling the bronchial airway during bronchoscopies in screening populations at high risk for lung cancer has increased detection of squamous bronchial pre-malignant lesions (PML). The majority of these lesions will regress or remain stable without any clinical intervention. However, a subset of lesions will progress to invasive malignancy. In this work, we investigate the gene expression changes in epithelial cell states and immune cell proportion shifts associated with premalignant histologic stage using single-cell RNA sequencing to begin to identify molecular features associated with PML regression or progression. Methods: Cells (n=3,325) were isolated from 11 endobronchial biopsies from 9 patients, where biopsy histology range from normal, dysplasia, carcinoma in situ (CIS) and squamous cell carcinoma. Immune cells (CD45+) and epithelial cells (CD45− EPCAM+) were sorted into separate 96-well plates using fluorescence activated cell sorting (FACS) and sequenced using CEL-Seq2 single cell RNA seq protocol. Results: After filtering low quality cells, we profiled 2,998 cells (1,052 CD45+ and 1,946 CD45−) with an average of 1,190 genes per cell. Within the epithelial cells, we focused on basal cells as they are the airway progenitor cells. We observed distinct differences in expression of KRT5+ (basal) cells between different histologic grades, where KRT5+ cells present in a hyperplasic lesion expressed multiple secretory cell markers suggesting they were transitioning to a secretory cell phenotype and KRT5+ cells from a CIS lesion from a current smoker expressed higher levels of smoking inducible genes, such as GSTM1 and CYP1A1. Lastly, KRT5+ cells from a lung squamous carcinoma tumor expressed higher levels of many genes related to cell cycle progression. Among the immune populations, low-grade PMLs with non-dysplastic histology were enriched for CD8+ T cells, whereas higher-grade PMLs and an invasive tumor were enriched for myeloid cells. Conclusions: To date, we have begun to identify histology-associated cellular and molecular profiles in bronchial premalignancy and early-stage carcinoma. Future resampling of these patients and expansion of cases will allow us to discover biomarkers associated with lesion progression and molecular targets for lung cancer interception. Citation Format: Conor Shea, Lukas Kalinke, Kitty De Jong, Kate Gowers, Diane Ding, Sherry Zhang, Gang Liu, Jack Cunningham, Ipsita Dey-Guha, Mark Hennon, Sai Yendumuri, Christopher Stevenson, Steven Dubinett, Avrum Spira, Marc Lenburg, Samuel Janes, Mary Reid, Jennifer Beane, Sarah Mazzilli, Joshua D. Campbell. Cellular and molecular changes associated with lung squamous premalignant lesion severity identified by single-cell RNA-seq [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2212.
Stem Cell Biology: A View toward the Future (2005)

In this essay I have attempted to provide clues relating to novel research avenues that are likely to have a broad impact on the field of stem cell biology. The specific examples, drawn from other areas, are meant to be instructive and are representative of many more similar efforts. I have suggested that the new areas of systems and synthetic biology may provide a truly deep level of understanding for many aspects of how stem cells make fate choices. Successful application of new avenues will require an integrative approach that combines experimental and computational techniques.
New pixel circuits for controlling threshold voltage by back‐gate bias voltage using crystalline oxide semiconductor FETs (2015)

Abstract We devised a threshold voltage compensation pixel circuit using back‐gate bias voltage. Variation in threshold voltages can be reduced to 10% in simulation while improving the saturation characteristics of a driving transistor. The pixel circuit can compensate not only threshold variation but also mobility variation. We fabricated a 5.29‐in Quad‐VGA organic light emitting diode display using this pixel circuit.
Multi-electron transfer enabled by topotactic reaction in magnetite (2019)

A bottleneck for the large-scale application of today's batteries is low lithium storage capacity, largely due to the use of intercalation-type electrodes that allow one or less electron transfer per redox center. An appealing alternative is multi-electron transfer electrodes, offering excess capacity, which, however, involves conversion reaction; according to conventional wisdom, the host would collapse during the process, causing cycling instability. Here, we report real-time observation of topotactic reaction throughout the multi-electron transfer process in magnetite, unveiled by in situ single-crystal crystallography with corroboration of first principles calculations. Contradicting the traditional belief of causing structural breakdown, conversion in magnetite resembles an intercalation process-proceeding via topotactic reaction with the cubic close packed oxygen-anion framework retained. The findings from this study, with unique insights into enabling multi-electron transfer via topotactic reaction, and its implications to the cyclability and rate capability, shed light on designing viable multi-electron transfer electrodes for high energy batteries.
Reduced Wafer-Scale Frequency Variation in Adiabatic Microring Resonators (2014)

We experimentally demonstrate that adiabatic microring resonators not only achieve high quality factors in the presence of electrical contacts but, importantly, exhibit reduced susceptibility to wafer-scale fabrication induced resonant frequency variations compared to standard microrings.
The Disillusioned Comfort with COVID-19 and the Potential of Convalescent Plasma and Cell Therapy (2020)

Coronavirus disease 2019 or COVID-19 is highly infectious, which can lead to acute and chronic debilitating symptoms, as well as mortality. The advent of safe and effective vaccines or antiviral drugs remains distant in the future. Practical public health measures, such as social distancing, hand washing, and wearing a face mask, are the current recommended guidelines by the Centers for Disease Control and Prevention for limiting the spread of the virus. Weakened immune system and aberrant inflammation represent a major pathological symptom of COVID-19 patients. Based on the unique immunomodulatory properties of both convalescent plasma and stem cells, we discuss here their potential use for treating COVID-19.
Role ofgyrAmutation and loss of OprF in the multiple antibiotic resistance phenotype ofPseudomonas aeruginosaG49 (1996)

A clinical isolate of Pseudomonas aeruginosa G48, became resistant during fluoroquinolone treatment giving rise to the post-therapy isolate, G49. To determine whether mutation in gyrA gave rise to fluoroquinolone resistance, G49 was transformed with a plasmid encoding gyrA (pNJR3-2); this reduced the MIC of fluoroquinolones for G49 two-fold. DNA sequencing of gyrA of G49 demonstrated a mutation at Thr-83, substituting with isoleucine. The outer membrane of G49 was shown to lack OprF, suggesting that loss of this protein may be involved in the multiple antibiotic resistance phenotype; however, when G49 was transformed with a plasmid encoding oprF (pRW5), expression of oprF was shown to have no effect upon the phenotype.
GRP nerves in pig antrum: role of GRP in vagal control of gastrin secretion (1987)

We extracted gastrin-releasing peptide (GRP) and its C-terminal decapeptide corresponding to 6.4 and 6.8 pmol/g from pig antrum mucosa. By immunohistochemistry GRP was localized to mucosal, submucosal, and myenteric nerve fibers. A few nerve cell bodies were also identified. Using isolated perfused pig antrum with intact vagal innervation, we found concomitant, atropine-resistant release of GRP and gastrin during electrical stimulation of the vagal nerves. Intra-arterial GRP at 10(-11)-10(-10) mol/l caused up to fivefold, dose-dependent increases in gastrin secretion; higher doses were less effective and completely desensitized the gastrin cells for the lower doses. After desensitization, vagal stimulation no longer produced gastrin secretion. The substance P antagonist [D-Arg, D-Pro, D-Trp, Leu]-substance P, described as also antagonizing the actions of bombesin, decreased the gastrin response to GRP and abolished the effect of vagal stimulation. The available evidence strongly suggests that GRP nerves are responsible for the stimulatory vagal effects on gastrin secretion in the pig.
Structural Basis of Specificity and Degeneracy of T Cell Recognition: Pluriallelic Restriction of T Cell Responses to a Peptide Antigen Involves Both Specific and Promiscuous Interactions Between the T Cell Receptor, Peptide, and HLA-DR (1998)

TCR engagement of peptide-MHC class II ligands involves specific contacts between the TCR and residues on both the MHC and peptide molecules. We have used molecular modeling and assays of peptide binding and T cell function to characterize these interactions for a CD4+ Th1 cell clone, ESL4.34, which recognizes a peptide epitope of the herpes simplex type 2 virus virion protein, VP16 393-405, in the context of several HLA-DR alleles. This clone responded to VP16 393-405 in proliferation and cytotoxicity assays when presented by DRB1*0402, DRB1*1102, and DRB1*1301, which share a common amino acid sequence, ILEDE, at residues 67-71 in the alpha-helical portion of the DRbeta polypeptide, but not when presented by other DR4, DR11, and DR13 alleles that are negative for this sequence. Using a panel of APCs expressing DR4 molecules that were mutagenized in vitro at individual residues within this shared epitope and using peptide analogues with single amino acid substitutions of predicted MHC and TCR contact residues, a unit of recognition was identified dependent on DRbeta residues 67-71 and relative position 4 (P4) of the VP16 393-405 peptide. The interactions of this portion of the peptide-DR ligand with the ESL4.34 TCR support a structural model for MHC-biased recognition in some Ag-specific and alloreactive T cell responses and suggest a possible mechanism for autoreactive T cell selection in rheumatoid arthritis.
Effects of Carnosine and Anserine Supplementation on Relatively High Intensity Endurance Performance (2006)

The purpose of this study was to investigate the effects of long-term chicken breast extract (CBEX) supplementation, a rich source of carnosine and anserine, on relatively high intensity endurance performance. Sixteen healthy male subjects were divided into CBEX group (n=8) and placebo group (n=8). The CBEX group was orally administered 200 ml CBEX drink which contained 4g of carnosine and anserine per day for 30 days. The placebo group was orally administered 200ml the same taste CBEX drink which contained no carnosine and anserine. Before and after the ingestion period, the subjects performed three sessions of consecutive endurance exercise (first session: 30-min at 50%VO2max; second session: 15-min at 75%VO2max; third session: until exhaustion at 100%VO2max) to measure exercise duration time at 100%VO2max, blood lactate concentration and ratings of perceived exertion (RPE) during the three sessions of consecutive endurance exercise. The exercise duration time at 100%VO2max was significantly increased after supplementation in the CBEX group. Blood lactate concentration and RPE at 75%VO2max was significantly decreased after supplementation in the CBEX group. These results suggest that the long-term ingestion of carnosine and anserine could enhance muscle buffering capacity, and in turn improve relatively high intensity endurance performance such as the so-called “last spurt” resulting from attenuation of the muscle fatigue at submaximal exercise.