gebhart/patrepeval huggingface dataset:
Cell–cell interaction networks regulate blood stem and progenitor cell fate (2009)

Communication networks between cells and tissues are necessary for homeostasis in multicellular organisms. Intercellular (between cell) communication networks are particularly relevant in stem cell biology, as stem cell fate decisions (self-renewal, proliferation, lineage specification) are tightly regulated based on physiological demand. We have developed a novel mathematical model of blood stem cell development incorporating cell-level kinetic parameters as functions of secreted molecule-mediated intercellular networks. By relation to quantitative cellular assays, our model is capable of predictively simulating many disparate features of both normal and malignant hematopoiesis, relating internal parameters and microenvironmental variables to measurable cell fate outcomes. Through integrated in silico and experimental analyses, we show that blood stem and progenitor cell fate is regulated by cell-cell feedback, and can be controlled non-cell autonomously by dynamically perturbing intercellular signalling. We extend this concept by demonstrating that variability in the secretion rates of the intercellular regulators is sufficient to explain heterogeneity in culture outputs, and that loss of responsiveness to cell-cell feedback signalling is both necessary and sufficient to induce leukemic transformation in silico.
On queueing in coded networks ¿ queue size follows degrees of freedom (2007)

We propose a new queueing mechanism for coded networks with stochastic arrivals and/or lossy links. In this context, earlier work introduced the notion of "virtual queues" which represent the backlog in degrees of freedom. For instance, the work by Ho and Viswanathan defined the achievable rate region for which the virtual queue size is stabilized, using intra-session coding. The queueing scheme that we propose here forms a natural bridge between the virtual queue size and the physical queue size, and thus extends their result to the stability of the physical queues as well. Specifically, we show that the amount of memory used at the transmit buffer in our scheme is upper bounded by the total backlog in the number of linearly independent degrees of freedom. Moreover, our scheme gives an online algorithm for queue update and coding, in the sense that the coding does not happen block by block, but in a streaming manner. The main idea in our scheme is to ensure that the information stored at the sender excludes any knowledge that is common to all receivers. This requires the transmitting node to track the states of knowledge of its receivers. Therefore, if the links are lossy, some form of feedback may be necessary.
Use of Nipponbare BAC Clones for Physical Mapping of an <i>R</i> Gene Locus in Rice (2006)

Major advances in rice genomics during the last few years have made positional cloning in rice much more efficient. Nipponbare is a model rice genotype being sequenced by the International Rice Genome Sequencing Project Consortium. Here, we describe an efficient procedure of the construction of physical map for positional cloning of resistance gene (R) using the Nipponbare genetic resources. This advanced strategy should be useful for the efficient identification of agronomic important R genes from many resistant rice genotypes, including wild rice species.
First-Principles Prediction of Liquid/Liquid Interfacial Tension (2014)

The interfacial tension between two liquids is the free energy per unit surface area required to create that interface. Interfacial tension is a determining factor for two-phase liquid behavior in a wide variety of systems ranging from water flooding in oil recovery processes and remediation of groundwater aquifers contaminated by chlorinated solvents to drug delivery and a host of industrial processes. Here, we present a model for predicting interfacial tension from first principles using density functional theory calculations. Our model requires no experimental input and is applicable to liquid/liquid systems of arbitrary compositions. The consistency of the predictions with experimental data is significant for binary, ternary, and multicomponent water/organic compound systems, which offers confidence in using the model to predict behavior where no data exists. The method is fast and can be used as a screening technique as well as to extend experimental data into conditions where measurements are technically too difficult, time consuming, or impossible.
Numerical Selection of Optimal Tumor Imaging Agents with Application to Engineered Antibodies (2001)

Three analytic indicators were used to compare five members of a monoclonal antibody (Mab) family. The cognates consisted of the genetically engineered intact chimeric IgGI (cT84.66) and related engineered fragments [scFv, diabody, minibody, F(ab')2] reactive against the same epitope of carcinoembryonic antigen (CEA). All analyses were based on radioiodinated Mabs targeting to colorectal xenografts of LS174T tumors in nude mice. Affinity constants were evaluated initially. A second indicator was the imaging figure of merit (IFOM) which determines how rapidly a statistically significant tumor image can be acquired. Finally, deconvolution was used to determine tumor temporal response to an arterial bolus. This last analysis gave the possible tumor accumulation in the absence of normal tissue sequestration. Affinities were all in excess of 10(8) M-1 and were highest for the divalent Mabs. Using the IFOM criterion, an 131I label was best suited as a radiolabel for the intact (IgG) T84.66, while an 123I label indicated optimal imaging with either minibody or F(ab')2. Deconvolution analyses showed that divalent members behaved similarly while the univalent member (scFv) had a tumor residence time smaller by an order of magnitude. The diabody had the largest impulse response function, but renal uptake may limit its present usefulness.
Lead Optimization of 5-Aryl Benzimidazolone- and Oxindole-Based AMPA Receptor Modulators Selective for TARP γ-8 (2018)

Glutamate mediates fast excitatory neurotransmission via ionotropic α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. The trafficking and gating properties of AMPA receptors (AMPARs) can be amplified by transmembrane AMPAR regulatory proteins (TARPs), which are often expressed in localized brain regions. Herein, we describe the discovery, lead optimization, and preclinical characterization of 5-arylbenzimidazolone and oxindole-based negative modulators of AMPARs associated with TARP γ-8, the primary TARP found in hippocampus. High-throughput screen lead <b>4</b> was optimized for potency and brain penetration to provide benzimidazolone <b>3</b>, JNJ-55511118.1 Replacement of the benzimidazolone core in <b>3</b> with an oxindole mitigated reactive metabolite formation and led to the identification of <b>18</b> (GluA1/γ-8 pIC<sub>50</sub> = 9.7). Following oral dosing in rats, <b>18</b> demonstrated robust target engagement in hippocampus as assessed by <i>ex vivo</i> autoradiography (ED<sub>50</sub> = 0.6 mg/kg, plasma EC<sub>50</sub> = 9 ng/mL).
Abstract 511: An assessment of pre-conditioning regimens for optimal hCD34+ hematopoietic stem cell humanization of NSGTMmice (2019)

Abstract Humanized immune system (HIS) mice - immunocompromised Nod.Cg-Prkdcscid Il2rgtm1Wjl/SzJ animals in which the immune system has been humanized by the engraftment of CD34+ hematopoietic stem cells (HSC), peripheral blood mononuclear cells (PBMC), or other human cells/tissues - represent an important tool in pre-clinical oncology research. Here we investigated several pre-conditioning regimens (Busulfan pre-treatment or total body irradiation (TBI)) to determine which would yield maximum human leukocyte engraftment and lineage diversity. Animals were pre-treated either one or two doses of Busulfan (25 mg/kg) or varying doses of TBI (1.75, 2.0, or 2.5 Gy). One to two days later, animals received an adoptive transfer of native hCD34+ HSCs. Engraftment was monitored by flow cytometry assessment of peripheral blood four weeks after adoptive-transfer, and every four weeks thereafter through experiment termination at Week 16. Upon termination, spleen and bone-marrow were assessed for various leukocyte populations by flow cytometry. Animals undergoing pre-conditioning displayed increased human CD45+ cell engraftment at all timepoints as compared to animals without pre-conditioning, with animals treated with two doses of Busulfan demonstrating the greatest human CD45+ engraftment at all timepoints and reaching statistical significance at endpoint (vs no pre-conditioning; p&amp;lt;0.05). Diversity of leukocyte cell types (B cells, T cells, NK cells, and other hCD45+) in the bone-marrow was similar across pre-treatment paradigms, however for some lineages, representation in the bone-marrow was significantly altered between pre-conditioning type. The absolute number of T or B cells were increased in TBI and Busulfan treated groups, respectively, whereas NK cells as a percentage of singlets were increased in TBI treated groups. The diversity of leukocyte cell types in the spleen was likewise similar across groups, with B cells dominating. These data provide important insights into the utility of various pre-conditioning regimens for the humanization of NSG mice for pre-clinical oncology research, and demonstrate that the optimum pre-conditioning regimens should be selected based on treatment target. Citation Format: Caitlin S. Parello, Benjamin G. Cuiffo, Alexandria Kury, Kasey Reardon, Brett Van Dam, Sallyann Vu, Catarina Costa, Veronica Ritchie, Gavin Gagnon, Timothy Bateson, Samantha Rogers, Gregory D. Lyng, Stephen T. Sonis. An assessment of pre-conditioning regimens for optimal hCD34+ hematopoietic stem cell humanization of NSGTMmice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 511.
Trends in fluorescence imaging and related techniques to unravel biological information (2007)

Optical microscopy is among the most powerful tools that the physical sciences have ever provided biology. It is indispensable for basic lab work, as well as for cutting edge research, as the visual monitoring of life processes still belongs to the most compelling evidences for a multitude of biomedical applications. Along with the rapid development of new probes and methods for the analysis of laser induced fluorescence, optical microscopy over past years experienced a vast increase of both new techniques and novel combinations of established methods to study biological processes with unprecedented spatial and temporal precision. On the one hand, major technical advances have significantly improved spatial resolution. On the other hand, life scientists are moving toward three- and even four-dimensional cell biology and biophysics involving time as a crucial coordinate to quantitatively understand living specimen. Monitoring the whole cell or tissue in real time, rather than producing snap-shot-like two-dimensional projections, will enable more physiological and, thus, more clinically relevant experiments, whereas an increase in temporal resolution facilitates monitoring fast nonperiodic processes as well as the quantitative analysis of characteristic dynamics.
Do Environmental and Economic Performance Go Together? A Review of Micro-level Empirical Evidence from the Past Decade or So (2019)

This article reviews the empirical literature combining economic and environmental performance data at the micro-level, i.e. firm or facility level. The literature has generally found a positive and statistically significant correlation between economic performance, as measured by profitability indicators or stock market returns, and environmental performance, as measured by emissions of pollutants or adoption of international environmental standards. The main reason for this finding seems to be that firms that reduce their material and energy costs experience both better economic performance and lower emissions. Only a small and recent literature analyses the joint causal impact of environmental regulations on environmental and economic performance. Interestingly, this literature shows that environmental regulations tend to improve environmental performance while not weakening economic performance. However, the evidence so far is limited to a handful of environmental regulations that are not extremely stringent, so the result cannot be easily generalized. More research is needed to assess the joint effects of environmental regulations on environmental and economic performance, to explore the heterogeneity of these effects across sectors, countries and types of policies, and to understand which policy designs allow improving environmental quality while not coming at a cost in terms of economic performance of regulated businesses.
Palm NMR and 1-Chip NMR (2010)

In our earlier work, we developed a 2-kg NMR system, which was 60 X lighter, 40× smaller, yet 60× more spin-mass sensitive than a 120-kg state-of-the-art commercial benchtop system. Here we report on two new nuclear magnetic resonance (NMR) systems that represent further orders-of-magnitude size reduction and lab-on-a-chip capability. The first system, which weighs 0.1 kg and can be held in the palm of a hand, is the smallest NMR system ever built, and is 1200× lighter, 1200× smaller, yet 150× more spin-mass sensitive than the commercial system. It is enabled by combining the physics of NMR with a CMOS RF transceiver. The second system, which even integrates a sample coil, directly interfaces the CMOS chip with a sample for lab-on-a-chip operation. The two systems detect biological objects such as avidin, human chorionic gonadotropin, and human bladder cancer cells.
An SU-8/Glass Meshed Patch Antenna for Integration with Solar Cells (2022)

In this paper, a wideband SU-8-based stacked meshed patch antenna is designed for integration with solar cells in CubeSats. The bottom meshed patch antenna is placed on glass substrate Corning 7070, and a thick layer of SU-8 negative photoresist serves as the upper patch substrate. The proposed antenna achieves a balanced compromise between the weight, robustness, transparency, and performance. The antenna bandwidth is 4.3%, from 2.376 GHz to 2.483 GHz, and the maximum gain in the entire frequency range is 5.3 dBi.
Splice variants of mitofusin 2 shape the endoplasmic reticulum and tether it to mitochondria (2023)

In eukaryotic cells, different organelles interact at membrane contact sites stabilized by tethers. Mitochondrial mitofusin 2 (MFN2) acts as a membrane tether that interacts with an unknown partner on the endoplasmic reticulum (ER). In this work, we identified the <i>MFN2</i> splice variant ERMIT2 as the ER tethering partner of MFN2. Splicing of <i>MFN2</i> produced ERMIT2 and ERMIN2, two ER-specific variants. ERMIN2 regulated ER morphology, whereas ERMIT2 localized at the ER-mitochondria interface and interacted with mitochondrial mitofusins to tether ER and mitochondria. This tethering allowed efficient mitochondrial calcium ion uptake and phospholipid transfer. Expression of ERMIT2 ameliorated the ER stress, inflammation, and fibrosis typical of liver-specific <i>Mfn2</i> knockout mice. Thus, ER-specific <i>MFN2</i> variants display entirely extramitochondrial MFN2 functions involved in interorganellar tethering and liver metabolic activities.
Behavioral Effects of CB2 Cannabinoid Receptor Activation and Its Influence on Food and Alcohol Consumption (2008)

Consumers of marijuana typically feel a strong, compulsive desire to consume food. Although past research revealed that the CB1 cannabinoid receptor is a potent regulator of food intake, the functional presence of neuronal CB2 cannabinoid receptors in the brain has been controversial. The role of CB2 receptors in food and alcohol consumption and the behavioral effects of CB2 receptor ligands are not well characterized. This is because CB2 cannabinoid receptors were thought to be absent from the brain and expressed primarily in immune cells and in the periphery. We tested the effects of peripheral injections of CB2 antagonist AM 630, CB2 agonist PEA, and CB1 antagonist AM 251 on male C57BL/6, Balb/c, and DBA/2 mice at the beginning of the night cycle and after overnight 12-hour fasts. We also investigated the effects of the putative CB2 agonist, JWH015, and CB2 antagonist, SR144528, in mouse motor function tests and in the two-compartment black and white box. Under standard conditions, the CB2 antagonist AM 630 inhibited food consumption in C57BL/6 mice and DBA/2 mice, but failed to block food intake of Balb/c mice. The CB2 agonist PEA had no significant effect on food consumption in Balb/c mice, and reduced food intake in C57BL/6 and DBA mice. The CB1 antagonist AM 251 inhibited food ingestion in the three mouse strains at variable times. After 12-hour food deprivation, the CB2 antagonist AM 630 increased food consumption in C57Bl/6 mice, but failed to produce significant changes in food intake for Balb/c and DBA/2 mice. The CB2 agonist PEA also reduced food consumption in all three mice strains at variable times. In comparison to the CB2 ligands, CB1 antagonist AM 251 inhibited food ingestion in the mouse strains. A general pattern of depression in locomotor activity was induced by JWH 015 in both males and females in the three mouse strains tested as the dose was increased. The development and enhancement of alcohol preference was observed after chronic treatment with CB2 agonist JWH 015 in stressed mice, but not in controls. In the DBA/2 strain, the spontaneous locomotor activity and stereotype behavior was enhanced by acute administration of low doses of SR144528. There was a reduction in CNR2 gene expression in the ventral mid-brain region of mice that developed alcohol preference, but not in those that did not develop alcohol preference. These effects of CB2 cannabinoid receptor ligands in in vivo behavioral tests are provided as functional evidence that CB2-Rs in the brain play a role in food and alcohol consumption and in the modification of mouse behavior.
Alternatives to HIST for acellular pertussis vaccines: progress and challenges in replacement. (2016)

The 'International Workshop on Alternatives to the Murine Histamine Sensitization Test for Acellular Pertussis Vaccines: Progress and Challenges in the Replacement of HIST' was held on 24 August 2014, in Prague, Czech Republic, as a satellite meeting to the 9th World Congress on Alternatives and Animal Use in the Life Sciences. Participants discussed the progress and challenges associated with the development, validation, and implementation of in vitro assays as replacements for the histamine sensitisation test (HIST) for acellular pertussis vaccines. Discussions focused on the consistency approach, the necessary framework for regulatory acceptance of a harmonised method, and recent international efforts towards the development of in vitro assays to replace the HIST. Workshop participants agreed that acceptable alternatives to the HIST should be based on ADP ribosylation-mediated cell intoxication and therefore that the CHO cell clustering assay, which measures cell intoxication, should be further pursued and developed as a possible replacement for the HIST. Participants also agreed to continue ongoing multinational discussions involving national and international standardisation authorities to reach consensus and to organise collaborative studies in this context for assay characterisation and calibration of reference materials.
Multiobject Tracking by Submodular Optimization (2018)

In this paper, we propose a new multiobject visual tracking algorithm by submodular optimization. The proposed algorithm is composed of two main stages. At the first stage, a new selecting strategy of tracklets is proposed to cope with occlusion problem. We generate low-level tracklets using overlap criteria and min-cost flow, respectively, and then integrate them into a candidate tracklets set. In the second stage, we formulate the multiobject tracking problem as the submodular maximization problem subject to related constraints. The submodular function selects the correct tracklets from the candidate set of tracklets to form the object trajectory. Then, we design a connecting process which connects the corresponding trajectories to overcome the occlusion problem. Experimental results demonstrate the effectiveness of our tracking algorithm. Our source code is available at https://github.com/shenjianbing/submodulartrack.
Maternal obesity alters offspring liver and skeletal muscle metabolism in early post‐puberty despite maintaining a normal post‐weaning dietary lifestyle (2022)

Maternal obesity (MO) during pregnancy is linked to increased and premature risk of age-related metabolic diseases in the offspring. However, the underlying molecular mechanisms still remain not fully understood. Using a well-established nonhuman primate model of MO, we analyzed tissue biopsies and plasma samples obtained from post-pubertal offspring (3-6.5 y) of MO mothers (n = 19) and from control animals born to mothers fed a standard diet (CON, n = 13). All offspring ate a healthy chow diet after weaning. Using untargeted gas chromatography-mass spectrometry metabolomics analysis, we quantified a total of 351 liver, 316 skeletal muscle, and 423 plasma metabolites. We identified 58 metabolites significantly altered in the liver and 46 in the skeletal muscle of MO offspring, with 8 metabolites shared between both tissues. Several metabolites were changed in opposite directions in males and females in both liver and skeletal muscle. Several tissue-specific and 4 shared metabolic pathways were identified from these dysregulated metabolites. Interestingly, none of the tissue-specific metabolic changes were reflected in plasma. Overall, our study describes characteristic metabolic perturbations in the liver and skeletal muscle in MO offspring, indicating that metabolic programming in utero persists postnatally, and revealing potential novel mechanisms that may contribute to age-related metabolic diseases later in life.
Design and Control of Park & Charge Lanes for Carsharing Services with Highly-Automated Electric Vehicles (2020)

Carsharing operators could benefit from vehicle automation even before full vehicle automation is available city-wide: so-called Park- & Charge Lanes (PCL) installed in closed environments can increase customer convenience and reduce costs for parking space and charging operations. The concept introduced in this study comprises the stacking of vehicles in several lanes of optimized width, the division of lanes into charging and parking areas, and control strategies for efficient operation. Compared to conventional parking lots with two lanes and two perpendicularly arranged parking spaces, the stacking of vehicles allows for space reductions of up to 43 %. Additional cost savings can be achieved, since it is not necessary to equip every parking space with an inductive charging plate. Splitting each lane into a parking and a charging area makes the optimal control problem non-trivial: In order to provide the vehicles with a battery level that is high enough to serve customer requests, the PCL has to be controlled in a smart way. Both rule-based and model-predictive control policies are developed for assigning arriving vehicles to lanes and selecting vehicles for customer requests. An event-based simulation framework is created in order to test the performance of the introduced policies for the resulting dynamic and stochastic PCL problem. The best of the four described rule-based policies performs nearly as good as the implemented model-predictive control approach in the numerical experiment. The model-predictive control policy outperforms the random lane selection by 27 %, which clearly refects the benefit of using advanced control strategies.