gebhart/patrepeval huggingface dataset:
Assessment and Challenges of Ligand Docking into Comparative Models of G-Protein Coupled Receptors (2013)

The rapidly increasing number of high-resolution X-ray structures of G-protein coupled receptors (GPCRs) creates a unique opportunity to employ comparative modeling and docking to provide valuable insight into the function and ligand binding determinants of novel receptors, to assist in virtual screening and to design and optimize drug candidates. However, low sequence identity between receptors, conformational flexibility, and chemical diversity of ligands present an enormous challenge to molecular modeling approaches. It is our hypothesis that rapid Monte-Carlo sampling of protein backbone and side-chain conformational space with Rosetta can be leveraged to meet this challenge. This study performs unbiased comparative modeling and docking methodologies using 14 distinct high-resolution GPCRs and proposes knowledge-based filtering methods for improvement of sampling performance and identification of correct ligand-receptor interactions. On average, top ranked receptor models built on template structures over 50% sequence identity are within 2.9 Å of the experimental structure, with an average root mean square deviation (RMSD) of 2.2 Å for the transmembrane region and 5 Å for the second extracellular loop. Furthermore, these models are consistently correlated with low Rosetta energy score. To predict their binding modes, ligand conformers of the 14 ligands co-crystalized with the GPCRs were docked against the top ranked comparative models. In contrast to the comparative models themselves, however, it remains difficult to unambiguously identify correct binding modes by score alone. On average, sampling performance was improved by 10(3) fold over random using knowledge-based and energy-based filters. In assessing the applicability of experimental constraints, we found that sampling performance is increased by one order of magnitude for every 10 residues known to contact the ligand. Additionally, in the case of DOR, knowledge of a single specific ligand-protein contact improved sampling efficiency 7 fold. These findings offer specific guidelines which may lead to increased success in determining receptor-ligand complexes.
Supplementary Figure S1-S3 from <i>In Vivo</i> Tracking of Adoptively Transferred Natural Killer Cells in Rhesus Macaques Using <sup>89</sup>Zirconium-Oxine Cell Labeling and PET Imaging (2023)

&lt;p&gt;Fig. S1. Zr-89 oxine labeling does not alter NK cell phenotype. Fig. S2. PET/CT reveals low bone marrow homing of NK cells. Fig. S3. CD34+ HSPCs home to the bone marrow.&lt;/p&gt;
Specific Antibody Responses to Vaccination with Bivalent CM235/SF2 gp120: Detection of Homologous and Heterologous Neutralizing Antibody to Subtype E (CRF01.AE) HIV Type 1 (2003)

HIV-1 CRF.AE-01 (formerly subtype E) infection is highly prevalent in Southeast Asia. Despite success with public health measures, the development of an effective CRF01.AE vaccine is critical to the control of this epidemic. Sera from the open-label arms of the first clinical trial of a bivalent HIV gp120 SF2/CM235 (subtypes B and CRF.AE-01, respectively) vaccine were evaluated for the presence of gp120-specific binding (BAb) and neutralizing antibody (NAb). Twelve pre- and postvaccination sera pairs were tested for CM235 BAb; anti-gp120 CM235 BAb was found in all postvaccination samples. The 12 pre- and postvaccination (1 month after third vaccination) serum pairs were evaluated in several neutralization formats: heterologous T cell line adapted (TCLA) NP03/H9, homologous CM235/PBMC, CM235/dendritic cell, and CM235M4-C4.6/A3R5. A3R5 is a CCR5+ T cell line, and CM235M4-C4.6 is the homologous CM235 virus adapted to growth in A3R5 cells. All volunteers developed BAb, but meaningful NAb was not demonstrable against primary isolate CM235. Using the TCLA CRF01.AE virus NP03 in H9 cells, 9 of 12 persons had NAb with a geometric mean titer (GMT) of 46. The CM235M4-C4.6 virus in A3R5 cells also detected NAb in 9 of 12 persons, with a GMT of 41. CM235M4-C4.6/A3R5 detected NAb in two persons with negligible NAb to NP03/H9 and vice versa. Whether the NAb detected by the CM235M4-C4.6/A3R5 system is qualitatively different from those in more traditional NP03/H9 assays will require further study.
Influence of FGF2 and PEG hydrogel matrix properties on hMSC viability and spreading (2009)

In this study, three-dimensional (3-D) poly(ethylene glycol) (PEG) hydrogel arrays were used to screen for the effects of fibroblast growth factor-2 (FGF2), combined with multiple hydrogel matrix parameters, on human mesenchymal stem cell (hMSC) viability and spreading. In particular, we examined the effects of FGF2 while co-varying hydrogel matrix degradability, cell adhesion ligand type, and cell adhesion ligand density. FGF2 significantly improved viability of hMSCs in a dose-dependent manner in both nondegrading and degrading PEG hydrogels in the absence of extracellular matrix-derived cell adhesion ligands. The presence of a small molecule that inhibits autophosphorylation of the FGF2 receptor blocked the effects of FGF2 on hMSC viability in PEG hydrogels, both in the presence and absence of the Arg-Gly-Asp-Ser-Pro (RGDSP) ligand. FGF2 effects on hMSC viability were less pronounced when FGF2 was presented in combination with the RGDSP cell adhesion ligand or the IKVAV cell adhesion ligand in nondegrading PEG hydrogels. Importantly, spread hMSC morphologies were observed and quantified in a select subset of hydrogel networks, which were degradable and included both FGF2 and RGDSP. These results indicate that the hydrogel arrays described here can be used to efficiently study the influence of soluble and insoluble hydrogel matrix parameters on stem cell behavior, and to identify synthetic, 3-D environments that promote specific hMSC behaviors.
Suppression of Murine IgE Responses with Ovalbumin-Pullulan Conjugates: Comparison of the Suppressive Effect of Different Conjugation Methods and Different Molecular Weights of Pullulan (1993)

Ovalbumin (OVA)-pullulan conjugates were made using four different conjugation methods and eight different molecular weights of pullulan ranging from 4,200 to 600,000. Pretreatment of mice by the administration of conjugates made by using cyanulic chloride or cyanogen bromide and pullulan of molecular weight 40,000 or more, anti-OVA IgE antibody response was suppressed completely and anti-OVA IgM and IgG antibody response was enhanced. In contrast, by the administration of conjugates made by using an oxidation or thiol activation method, only partial suppression of anti-OVA IgE antibody response was achieved and no enhancement of anti-OVA IgM and IgG antibody production was observed.
Mikrobiologische Galleanalyse und antibiotische Therapie: Eine prospektive Studie von 1401 ERCs (2010)

Einleitung: Eine Cholangitis ist eine regelmäßige Komplikation bei pathologischen Gallengangsveränderungen. Daten zu bakteriellen und fungalen Cholangitiden könnten das periinterventionelle Vorgehen verbessern.
Heavy End Evaluation in Oils and Associated Asphaltene Deposits from Two Adjacent Reservoirs by High-Resolution Mass Spectrometry (2022)

The formation of viscous oil and tar mats in oilfield reservoirs has substantial consequences in the production of oil. For example, aquifer sweep can be precluded in such an occurrence, impacting field development planning. Several processes can give rise to accumulations of heavy ends in reservoirs, namely, the asphaltenes and other high-molecular-weight polar compounds. Multiple, incompatible charge fluids can enter a reservoir, causing instability, migration, accumulation, and phase separation of heavy ends. Two adjacent reservoirs in Norway evidently exhibit different stages of tar formation from incompatible charge: in one reservoir, asphaltenes deposit as a result of an excess asphaltene concentration, and in the second reservoir, asphaltenes deposit from solution gas expulsion. Here, ultrahigh-resolution mass spectrometry is used to analyze heavy ends from both reservoirs in crude oils and rock core chips. The heavy ends or asphaltenes in crude oils and associated core deposits from each reservoir are analyzed and shown to be compositionally very similar. In addition, the two crude oils are examined by two-dimensional gas chromatography, confirming that the hydrocarbon liquid-phase components closely resemble one another. Importantly, there are only subtle chemical differences between heavy ends that underwent phase separation in the reservoir versus heavy ends that remained in the crude oil, a result that is consistent with heavy end chemical speciation and solvation characteristics. The combination of thermodynamic and compositional considerations proves to be very effective in elucidation of reservoir fluid geodynamic processes that have a significant impact on oil production.
Abstract PR05: Genome-scale CRISPR-Cas9 screening to identify essential genes and pathways in pancreatic cancer (2016)

Abstract Loss-of-function genetic screens in cancer cell lines permit the systematic interrogation of genes and pathways involved in cell proliferation and viability. The CRISPR-Cas9 system enables effective genome editing for perturbation of gene function. To identify genes that are essential for cancer cell proliferation and survival, we have optimized an approach for efficient genome-scale CRISPR-Cas9 pooled screening and performed negative-selection knock-out screens in 43 human cancer cell lines with diverse genetic and phenotypic features, including 8 pancreatic cancer cell lines. We report that CRISPR-Cas9 efficacy varies depending on the cell context and propose methods to effectively identify differential cancer dependencies across cell lines. Additionally, we identify a strong correlation between genomic copy number and perceived gene dependency, and further elucidate a gene-independent effect of CRISPR-Cas9 cutting. Using these screening data, we performed a detailed interrogation of gene and pathway dependencies in pancreatic cancer. Through integrative analysis of CRISPR-Cas9 screening results with RNA-interference and small molecule screening data, as well as DNA and RNA sequencing, we identified a high-confidence set of recurrently essential genes in pancreatic cancer, including several with associated biomarkers. Moreover, through pathway analyses of CRISPR-Cas9 screening data, we have identified a number of essential biologic processes including key metabolic and cell signaling pathways that may represent potential therapeutic avenues. In particular, we characterize the sterol regulatory element binding protein (SREBP) signaling pathway as a recurrent vulnerability in pancreatic cancer and credential this pathway as a potential therapeutic target. This abstract is also being presented as Poster A13 Citation Format: Andrew J. Aguirre, Wei Shao, Han Xu, Barbara Weir, Francisca Vazquez, Robin Meyers, Cheng-Zhong Zhang, Mihir Doshi, Glenn S. Cowley, Theodore Ewachiw, Zeshaan Rasheed, Todd R. Golub, Kimberly Stegmaier, Charles W. Roberts, Levi A. Garraway, Matthew Meyerson, Aviad Tsherniak, David E. Root, Peter J. Espenshade, William C. Hahn.{Authors}. Genome-scale CRISPR-Cas9 screening to identify essential genes and pathways in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr PR05.
When the BRANCHED network bears fruit: how carpic dominance causes fruit dimorphism in Aethionema (2018)

Life in unpredictably changing habitats is a great challenge, especially for sessile organisms like plants. Fruit and seed heteromorphism is one way to cope with such variable environmental conditions. It denotes the production of distinct types of fruits and seeds that often mediate distinct life-history strategies in terms of dispersal, germination and seedling establishment. But although the phenomenon can be found in numerous species and apparently evolved several times independently, its developmental time course or molecular regulation remains largely unknown. Here, we studied fruit development in Aethionema arabicum, a dimorphic member of the Brassicaceae family. We characterized fruit morph differentiation by comparatively analyzing discriminating characters like fruit growth, seed abortion and dehiscence zone development. Our data demonstrate that fruit morph determination is a 'last-minute' decision happening in flowers after anthesis directly before the first morphotypical differences start to occur. Several growth experiments in combination with hormone and gene expression analyses further indicate that an accumulation balance of the plant hormones auxin and cytokinin in open flowers together with the transcript abundance of the Ae. arabicum ortholog of BRANCHED1, encoding a transcription factor known for its conserved function as a branching repressor, may guide fruit morph determination. Thus, we hypothesize that the plasticity of the fruit morph ratio in Ae. arabicum may have evolved through the modification of a preexisting network known to govern correlative dominance between shoot organs.
Gastrotomy and whole bowel irrigation in iron poisoning (1991)

Ipecac and gastric lavage are questionable interventions for the overdose patient, and activated charcoal does not absorb iron. Gastrotomy and whole bowel irrigation have been described as unique interventions for this poisoning. We describe a patient who was treated with each of these. Because less than half of the iron was removed during surgery, and because the chelation requirement was modest, it is likely that whole bowel irrigation removed a significant amount of iron. We believe that this combined approach contributed to our patient's positive outcome.
Conversion of coal to gasoline in one single synthesis loop (1986)

The process scheme for the conversion of syngas to gasoline via methanol (MeOH) developed by Mobil consists in essence of two independent synthesis loops, a MeOH and a gasoline loop. The first is a conventional MeOH-plant which produces raw MeOH. The raw MeOH is evaporated into a second synthesis loop, the methanol to gasoline (MTG) synthesis. This scheme is already in commercial operation in New Zealand. The syngas is produced by steam reforming of natural gas. A further development of this technology based on integration of the two syntheses is demonstrated in the Topsoe-Integrated-Gasoline-Synthesis, TIGAS. The main difference between the two schemes is that in the TIGAS process, the two loops, the MeOH synthesis and the Mobil MTG-process, are integrated into one single synthesis loop without isolation of MeOH as an intermediate. This results in a simple flow scheme and, hence, in substantial savings in investments and energy consumption.
Forecasting of Breathing Events from Speech for Respiratory Support (2023)

When a patient using a breathing support system such as a portable oxygen concentrator (POC) talks, the flow of oxygen to the lungs is disturbed. The ideal moment to administer oxygen-rich air during talking would be the brief inhale moments between utterances. However, the detection of the inhale moment is difficult and the latency of the air transfer from the pump, through the hose, to the nasal cannula may be larger than the inspiratory period in normal speech. The prediction of the next inhale moment could be used to compensate the latency and therefore provide a significantly better support for a patient who needs oxygen-rich air but want to communicate normally. In this paper we provide the first evidence that it is possible to forecasts the next inhale moment from the speech of the talker using deep learning techniques. Breathing forecasting from speech has also other potential applications that we briefly discuss in the paper.
<title>Distributed laser Doppler velocimeter</title> (1993)

Classical LDV techniques permit the recovering of the flow profile at the expense of the movement of projection and recovery optics. This operation limits the performances of the LDV and extends the measurement time. The aim of this communication is to present a novel monobeam distributed laser Doppler velocimeter (DLDV) which permits the continuous recovery of the flow velocity at any point belonging to the light beam, without moving the collimating optics. The DLDV applies the low-coherence multiplexing technique to a backscattering reference-beam LDV scheme. The DLDV uses a very-short coherence source (a superluminescent diode) which feeds an unbalanced interferometer. The sensing arm of the interferometer is launched in the flow while the remote reference arm permits the user to interrogate different flow volumes. The scheme has been implemented by all-fiber components. Preliminary measurements were given on a laboratory hydraulic circuit. The DLDV can be used as a conventional LDV, to measure with high accuracy a flow velocity component in a point of the duct, or in a distributed mode, to recover the flow velocity profile along a duct cross-section. Profiles of the flow were recovered at different average velocity and the first results confirm the exceptional capabilities of the novel instrument.
The Closing Wedge Osteotomy for Thoracolumbar Deformity in Ankylosing Spondylitis (2006)

Unsatisfactory results, neurological deficits, and in some instances life-threatening complications have made patients and doctors hesitant to decide for surgery in ankylosing spondylitis (AS) (1–4). However, decisive progress in surgical technique has been made toward fewer complications, less operative trauma, and better quality of life after surgery (5–7). Somatosensory evoked potential (SSEP)-monitoring allows continuous control of some functions of the spinal cord during surgery. Emphasis in this report is given to the benefits of improved instrumentation systems and better imaging studies which have made preoperative assessment and surgery of the cervical spine in ankylosing spine safer and more successful. We report on 66 AS patients (mean age: 49.4 years; male:female: 58:8) with cervical disorders treated in our institution in the period between 1994 and 2003. The material comprised subaxial disorders in the form of kyphosis in 31 patients, fractures and posttraumatic deformity in 26 patients and atlantoaxial instability and/or dislocation C1/C2 in the remaining nine patients. Surgery resulted in excellent correction of the disturbed sagittal profile with adequate stability and restoration of a horizontal axis of vision. Loosening of the screws with loss of the correction was encountered in one patient of cervicothoracic osteotomy and was successfully restored after a revision surgery. No mortalities or cord dysfunction were encountered. However, the most serious complication, partial sensory and/or motor deficit of root origin, was seen in eight patients. The C8 root was involved in six patients, followed by the C5 root in the remaining two. Remission (four patients) or substantial recovery (three patients) occurred in seven patients during the first three months after surgery.
Engineering for patient safety: the clinically driven approach. (2005)

60 January/February 2005 With the introduction of new surgical techniques and instruments, more difficult operations can be achieved. The consequences are that surgery is becoming more complex and that surgeons are becoming more dependent on technology; this is especially the case in the field of minimally-invasive surgery. For the most part, instruments used by surgeons are developed by engineers. During the instrumentation development process, it is important that engineers and surgeons cooperate closely in a clinically driven approach. At the Man Machine System group of the Delft University of Technology, a program on Minimally Invasive Surgery (MIS) was started in 1997. The program has been executed in close cooperation with research hospitals. The development of new technologies to improve minimally invasive procedures starts with task analyses followed by problem assessments, instrument design, and evaluation of new technologies. Instruments for laparoscopy and arthroscopy have been developed using the clinically driven approach. More detailed information about the total research program can be found in Engineering for Patient Safety—Issues in Minimally Invasive Procedures.1
Activation of MrgC receptor inhibits N-type calcium channels in small-diameter primary sensory neurons in mice (2014)

Mas-related G-protein-coupled receptor subtype C (mouse MrgC11 and rat rMrgC), expressed specifically in small-diameter primary sensory neurons, may constitute a novel pain inhibitory mechanism. We have shown previously that intrathecal administration of MrgC-selective agonists can strongly attenuate persistent pain in various animal models. However, the underlying mechanisms for MrgC agonist-induced analgesia remain elusive. Here, we conducted patch-clamp recordings to test the effect of MrgC agonists on high-voltage-activated (HVA) calcium current in small-diameter dorsal root ganglion (DRG) neurons. Using pharmacological approaches, we show for the first time that an MrgC agonist (JHU58) selectively and dose-dependently inhibits N-type, but not L- or P/Q-type, HVA calcium channels in mouse DRG neurons. Activation of HVA calcium channels is important to neurotransmitter release and synaptic transmission. Patch-clamp recordings in spinal cord slices showed that JHU58 attenuated the evoked excitatory postsynaptic currents in substantia gelatinosa (SG) neurons in wild-type mice, but not in Mrg knockout mice, after peripheral nerve injury. These findings indicate that activation of endogenously expressed MrgC receptors at central terminals of primary sensory fibers may decrease peripheral excitatory inputs onto SG neurons. Together, these results suggest potential cellular and molecular mechanisms that may contribute to intrathecal MrgC agonist-induced analgesia. Because MrgC shares substantial genetic homogeneity with human MrgX1, our findings may suggest a rationale for developing intrathecally delivered MrgX1 receptor agonists to treat pathological pain in humans and provide critical insight regarding potential mechanisms that may underlie its analgesic effects.
Evaluation of Parenteral Depot Insulin Formulation using PLGA and PLA Microparticles (2008)

PLGA and PLA microparticles entrapping insulin are prepared by solvent evaporation method and are evaluated in diabetes-induced rat for its efficacy in maintaining blood sugar level from a single intramuscular dose. In vitro release of insulin from PLGA and PLA microparticles are 75.35 +/- 1.73% and 67.536 +/- 2.23%, respectively in 168 h (7 days). Released insulin from polymer particles are mostly in monomeric form without aggregation. Optimal use of stabilizers during particle formulation helps in reducing protein denaturation and thus results in stabilized insulin-loaded polymer particles. Intramuscular administration of insulin-loaded PLGA (50 : 50) and PLA microparticles (equivalent to 25 IU insulin/kg of animal weight) in alloxaninduced diabetic rats result in 53.86 +/- 4.2% and 39.52 +/- 6.7% reduction in blood glucose level, respectively in 96 h. This effect continued up to 7 days in case of PLGA and PLA microparticles.
Thermal performance of dual piezoelectric cool jet for ultra-thin mobile applications (2014)

In order to dissipate heat from future low form factor microelectronic systems the use of piezoelectric blowers has recently attracted a great deal of attention. These zero-mass flow devices comprised of two piezoelectric membranes, whose oscillation frequency and amplitude can be electrically tuned, provide a net positive momentum which can be used to actively cool various device components. In order to evaluate the potential use of these cooling devices an open-air bench system has been developed. Experimental performance of a piezoelectric cooling device is compared to natural convection over a heated surface with an attached heat sink. Furthermore the convective heat transfer rate displays a maximum value at a certain threshold which corresponds with previously reported computational results.