gebhart/patrepeval huggingface dataset:
Effects of intracellular communication between T helper cells on Th2 differantiation (P1149) (2013)

Abstract Cytokines provide a main regulatory mechanism of immune responses, which allows for intercellular communication and enables cells to make collective decisions. Existing evidence for stochastiticity in expression of cytokines and their receptors raises the question: how does cytokine communication performs reliably in the face of noise? We study the effect of heterogeneity in IL4R expression level during Th2 differentiation as a model system. Naïve CD4 T cells were separated into different groups according to their IL4R expression levels and the different groups were cultured separately, under different IL4 concentrations driving their differentiation. Expression levels of Th2 markers, IL4 and GATA3, were measured at the single cell level. Our results reveal differences in the differentiation abilities of the different groups - higher initial receptor levels facilitate faster Th2 differentiation, at lower levels of IL4 as an input. Interestingly, we found that these differences in the differentiation abilities vanish when cells with high and low initial IL4R levels are co-cultured. These results suggest that intercellular interactions can decrease the potential heterogeneity in the population that results from noise in gene expression. These experiments provide an opportunity to evaluate the importance and roles played by intercellular communication in Th cell differentiation, and to assess the effects of stochasticity in protein levels on the differentiation process.
Loss of Proteostatic Control as a Substrate for Atrial Fibrillation: A Novel Target for Upstream Therapy by Heat Shock Proteins (2012)

Atrial fibrillation (AF) is the most common, sustained clinical tachyarrhythmia associated with significant morbidity and mortality. AF is a persistent condition with progressive structural remodeling of the atrial cardiomyocytes due to the AF itself, resulting in cellular changes commonly observed in aging and in other heart diseases. While rhythm control by electrocardioversion or drug treatment is the treatment of choice in symptomatic AF patients, its efficacy is still limited. Current research is directed at preventing first-onset AF by limiting the development of substrates underlying AF progression and resembles mechanism-based therapy. Upstream therapy refers to the use of non-ion channel anti-arrhythmic drugs that modify the atrial substrate- or target-specific mechanisms of AF, with the ultimate aim to prevent the occurrence (primary prevention) or recurrence of the arrhythmia following (spontaneous) conversion (secondary prevention). Heat shock proteins (HSPs) are molecular chaperones and comprise a large family of proteins involved in the protection against various forms of cellular stress. Their classical function is the conservation of proteostasis via prevention of toxic protein aggregation by binding to (partially) unfolded proteins. Our recent data reveal that HSPs prevent electrical, contractile, and structural remodeling of cardiomyocytes, thus attenuating the AF substrate in cellular, Drosophila melanogaster, and animal experimental models. Furthermore, studies in humans suggest a protective role for HSPs against the progression from paroxysmal AF to persistent AF and in recurrence of AF. In this review, we discuss upregulation of the heat shock response system as a novel target for upstream therapy to prevent derailment of proteostasis and consequently progression and recurrence of AF.
Fracture healing in protease‐activated receptor‐2 deficient mice (2012)

Protease-activated receptor-2 (PAR-2) provides an important link between extracellular proteases and the cellular initiation of inflammatory responses. The effect of PAR-2 on fracture healing is unknown. This study investigates the in vivo effect of PAR-2 deletion on fracture healing by assessing differences between wild-type (PAR-2(+/+)) and knock-out (PAR-2(-/-)) mice. Unilateral mid-shaft femur fractures were created in 34 PAR-2(+/+) and 28 PAR-2(-/-) mice after intramedullary fixation. Histologic assessments were made at 1, 2, and 4 weeks post-fracture (wpf), and radiographic (plain radiographs, micro-computed tomography (µCT)) and biomechanical (torsion testing) assessments were made at 7 and 10 wpf. Both the fractured and un-fractured contralateral femur specimens were evaluated. Polar moment of inertia (pMOI), tissue mineral density (TMD), bone volume fraction (BV/TV) were determined from µCT images, and callus diameter was determined from plain radiographs. Statistically significant differences in callus morphology as assessed by µCT were found between PAR-2(-/-) and PAR-2(+/+) mice at both 7 and 10 wpf. However, no significant histologic, plain radiographic, or biomechanical differences were found between the genotypes. The loss of PAR-2 was found to alter callus morphology as assessed by µCT but was not found to otherwise effect fracture healing in young mice.
A simple leakage drain current model for accumulation-mode SOI nMOSFETs operating up to 300°C (2001)

In this paper we present and discuss, a new leakage drain current model for accumulation-mode SOI pMOSFETs operating from temperature up to 300C.This model takes into consideration the channel length and the temperature of operation, and it is observed that the leakage drain current strongly depends on the drain voltage and the channel length increases. To support all the work, experimental results and bidimensional simulations were performed and compared.
385. Gene Correction in the Absence of DNA Repair: A Universal Model Involving Homologous Pairing and DNA Replication (2005)

Our laboratory has been studying the mechanism and regulation of targeted gene repair in mammalian cells. Using a robust cell line where the genomic correction frequencies average 1%, we have been able to modulate the process of DNA replication and observe its effect on the gene repair reaction. In our hands, gene correction occurs predominantly in S phase cells especially when the movement of the replication fork is delayed. Reminiscent of its role in homeologous recombination, several labs, including ours, have observed that the mismatch repair pathway appears to interfere with gene repair activity. Taking all of these observations into consideration, we now propose a universal model for gene repair in which the oligonucleotide becomes incorporated into the newly synthesized daughter strand at or near a stalled replication fork. Assimilation of the oligonucleotide creates a single mismatched base pair which, in the case of a MMR-deficient cell line, is tolerated through a single round of replication. During a second round, the replication machinery uses the oligonucleotide as the parental template and synthesizes the second strand of a fully converted allele. This model explains a multitude of unrelated observations that surround the variability of this technique. The integrated model of gene repair will be presented with examples from yeast and mammalian cells that strongly support its validity.
Effect of molecular p-doping on hole density and mobility in poly(3-hexylthiophene) (2012)

Employing impedance spectroscopy, we have studied the hole density, conductivity, and mobility of poly(3-hexylthiophene), P3HT, doped with the strong molecular acceptor tetrafluorotetracyanoquinodimethane, F4TCNQ. We find that the hole density increases linearly with the F4TCNQ concentration. Furthermore, the hole mobility is decreased upon doping at low-to-medium doping level, which is rationalized by an analytic model of carrier mobility in doped organic semiconductors [V. I. Arkhipov, E. V. Emelianova, P. Heremans, and H. Bässler, Phys. Rev. B 72, 235202 (2005)]. We infer that the presence of ionized F4TCNQ molecules in the P3HT layer increases energetic disorder, which diminishes the carrier mobility.
Towards Representation Learning for Atmospheric Dynamics (2021)

The prediction of future climate scenarios under anthropogenic forcing is critical to understand climate change and to assess the impact of potentially counter-acting technologies. Machine learning and hybrid techniques for this prediction rely on informative metrics that are sensitive to pertinent but often subtle influences. For atmospheric dynamics, a critical part of the climate system, no well established metric exists and visual inspection is currently still often used in practice. However, this "eyeball metric" cannot be used for machine learning where an algorithmic description is required. Motivated by the success of intermediate neural network activations as basis for learned metrics, e.g. in computer vision, we present a novel, self-supervised representation learning approach specifically designed for atmospheric dynamics. Our approach, called AtmoDist, trains a neural network on a simple, auxiliary task: predicting the temporal distance between elements of a randomly shuffled sequence of atmospheric fields (e.g. the components of the wind field from reanalysis or simulation). The task forces the network to learn important intrinsic aspects of the data as activations in its layers and from these hence a discriminative metric can be obtained. We demonstrate this by using AtmoDist to define a metric for GAN-based super resolution of vorticity and divergence. Our upscaled data matches both visually and in terms of its statistics a high resolution reference closely and it significantly outperform the state-of-the-art based on mean squared error. Since AtmoDist is unsupervised, only requires a temporal sequence of fields, and uses a simple auxiliary task, it has the potential to be of utility in a wide range of applications.
Wind Diesel Hybrid Power System with Hydrogen Storage (2013)

By 2050 the demand for energy could double or even triple as the global population grows and developing countries expand their economies. Energy prices, supply uncertainties, and environmental concerns are driving many countries to rethink their energy mix. The Inter‐ national Energy Agency’s Energy Technology Perspectives2008publication projects that en‐ ergy sector emissions of greenhouse gases (GHGs) will increase by 130% over 2005 levels, by 2050, in the absence of new policies (IEA, 2008).
High-Performance Rubber Sealant for Preventing Water Leaks (2010)

Considerable amounts of water are being lost due to leaks. One of the main reasons for experiencing such large water leaks is the premature failure of rubber sealants in valves. Water leaks commonly originate from the presence of chlorine ions in tap water. Here, we demonstrate that the incorporation of surface-modified and highly crystalline carbon nanotubes allows the rubber sealants to maintain their sealing properties without experiencing any distinctive degradation over a wide range of temperature and environmental conditions over their expected lifetime. It is envisaged that environmentally friendly nanotechnology will save huge amounts of energy for purifying and transporting water around the whole world.
ChemInform Abstract: 4‐Aminopiperidine Ureas as Potent Selective Agonists of the Human β<sub>3</sub>‐Adrenergic Receptor (2002)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.
Plasmonic Focusing in Symmetry Broken Nanocorrals (2010)

Plasmonic focusing was investigated in symmetry broken nanocorrals under linearly polarized illumination. Near-field optical measurements of the perpendicular electric field show that a single subwavelength spot size of 320 nm can be generated. The interference pattern within the corral can be controlled by changing the polarization of optical excitation and the degree of symmetry breaking. The intensity enhancement factor was investigated using finite-difference time-domain simulations and confirmed by analytical calculations taking into account the plasmon damping and multiple reflections against the corral wall.
A new strategy for tumor antigen discovery based on in vitro priming of naive T cells with dendritic cells. (2001)

We describe a method for discovery of new tumor antigens that uses dendritic cells (DCs) as antigen-presenting cells to prime autologous naive CD4+ and CD8+ T cells from healthy donors against tumor proteins and peptides. For the identification of HLA class I-restricted tumor antigens, peptides were extracted from tumor HLA class I molecules, fractionated by reverse phase-high performance liquid chromatography, and loaded onto in vitro-generated DCs to prime naïve CD8+ T cells. Our results show that we were able to prime naive CD8+ T cells in vitro to several peptide fractions and generate specificity for the tumor. Electrospray ionization mass spectrometry was used to confirm that these fractions contained peptides derived from MHC class I molecules, and the primed CD8+ T cells were used to further analyze the immunostimulatory peptide fractions. For the identification of HLA class II-restricted tumor antigens, we fractionated tumor protein extracts using reverse phase-high performance liquid chromatography and loaded individual fractions onto DCs to prime naive CD4+ T cells. Our results show that we were also able to prime naive CD4+ T cells to several protein fractions and generate specificity for the tumor. These results illustrate the potential of this method to identify new immunostimulatory MHC class I- and class II-restricted tumor antigens.
Switching of Soliton States in an Integrated 30 GHz Soliton Microcomb Source (2020)

Rich soliton formation dynamics via self-injection locking in an integrated microcomb source is studied. We demonstrate tuning of soliton repetition rate, switching of soliton states. The phase noise of soliton beatnote microwave signals is measured.
Sex-related differences in the regulation of macrophage cholesterol metabolism (2001)

Men have an earlier onset and higher incidence of coronary heart disease than women, independent of environmental risk factor exposure. As a consequence, there has been considerable interest in the potential role of sex hormones in atherogenesis. An emerging body of evidence suggests that sex-specific tissue and cellular characteristics may mediate sex-specific responses to a variety of stimuli. Recent studies have shown that oestrogen, progesterone and androgens all regulate processes integral to human macrophage foam cell formation, a key event in atherogenesis, in a sex-specific manner; findings that may have important implications for understanding the sex gap in atherosclerosis. Physiological levels of 17beta-estradiol and progesterone are both associated with a female-specific reduction in cholesteryl ester accumulation in human macrophages. By contrast, androgens increase cholesteryl ester formation in male but not in female donor human macrophages. This review summarizes current data concerning the sex-specific effects of sex hormones on processes important to macrophage foam cell formation and the basic mechanisms responsible for the sex specificity of such effects. Future research in this promising field may eventually lead to the novel concept of 'sex-specific' treatments directed at inhibiting atherogenesis.
Status of lifestyle modifications in hypertension. (2001)

Hypertension is essentially the elevation of arterial blood pressure beyond an arbitrary cut off point, though the dividing line between normal and elevated BP is lacking. Hypertension can be classified into primary, essential or idiopathic hypertension on one hand, and secondary one due to some disease itself. In treating hypertension, antihypertensives have their role, but attention may be directed towards some lifestyle modifications. As regarding dietary interventions, calorie restriction may influence the minimisation of BP. Body weight reduction, less alcohol consumption, salt restriction, potassium and calcium supplementation can enhance the process of lowering BP. The role of magnesium in hypertension is debatable. Serum cholesterol level is commonly elevated in hypertensive patients and its reduction reduces the risk of non-fatal coronary events. Diet rich in plant fibres either alone or with a low fat, low sodium could lower the BP by about 5 mm Hg in hypertensives. The omega-3-polyunsaturated fatty acids found in highest concentrations in cold water fishes have a modest antihypertensive effect. Caffeine contained in two cups of coffee may raise the BP by 5 mm Hg in infrequent users but in habitual users, caffeine has no role. Deficiency of vitamin C might lead to hypertension. As regarding behavioural changes, stopping smoking, regular physical exercise, relaxation therapies like yoga, etc, have definite beneficial effect on hypertensives. The antihypertensive effect of lifestyle modifications may obviate drug therapy. For this one or more of the lifestyle modifications should be tried initially in all hypertensive patients.
Supplemental figure 5. Combined PIM/MEK inhibition restores sensitivity to AZD1208 in NF1 knock out cell lines from PIM Kinases Are a Potential Prognostic Biomarker and Therapeutic Target in Neuroblastoma (2023)

&lt;p&gt;(A-F) The indicated cell lines were plated in 6-well plates and treated with AZD1208, cobimetinib, MK2206 or the combination. Drug-containing medium was refreshed every 3 days. Cells were fixed, stained, and scanned when untreated wells reached confluency (n=3).&lt;/p&gt;
Supplementary Figure S1 from &lt;i&gt;BRCA1&lt;/i&gt; Mutation Analysis of 41 Human Breast Cancer Cell Lines Reveals Three New Deleterious Mutants (2023)

Supplementary Figure S1 from &lt;i&gt;BRCA1&lt;/i&gt; Mutation Analysis of 41 Human Breast Cancer Cell Lines Reveals Three New Deleterious Mutants
FollowMe: Efficient Online Min-Cost Flow Tracking with Bounded Memory\n and Computation (2014)

One of the most popular approaches to multi-target tracking is\ntracking-by-detection. Current min-cost flow algorithms which solve the data\nassociation problem optimally have three main drawbacks: they are\ncomputationally expensive, they assume that the whole video is given as a\nbatch, and they scale badly in memory and computation with the length of the\nvideo sequence. In this paper, we address each of these issues, resulting in a\ncomputationally and memory-bounded solution. First, we introduce a dynamic\nversion of the successive shortest-path algorithm which solves the data\nassociation problem optimally while reusing computation, resulting in\nsignificantly faster inference than standard solvers. Second, we address the\noptimal solution to the data association problem when dealing with an incoming\nstream of data (i.e., online setting). Finally, we present our main\ncontribution which is an approximate online solution with bounded memory and\ncomputation which is capable of handling videos of arbitrarily length while\nperforming tracking in real time. We demonstrate the effectiveness of our\nalgorithms on the KITTI and PETS2009 benchmarks and show state-of-the-art\nperformance, while being significantly faster than existing solvers.\n
Potential Therapeutic Agents from the Red Sea Organisms (2014)

In the last few decades, the pharmaceutical application of marine natural products has attracted much attention from both organic and medicinal chemists. Recently, significant interest is focused on the isolation, identification, and biological activities of compounds from the Red Sea organisms and many of these compounds show promising biological activities, particularly cytotoxic and antimicrobial effects. This review covers the natural products and their biological activities isolated from the Red Sea flora and fauna in the recent past years.
T-help, TRAIL, and CTL memory (2006)

Cytotoxic CD8+ T lymphocytes (CTLs) are especially suited to the detection and eradication of incipient tumors due to their capacity to recognize neoplastic cells based on the mutated, over-expressed or tissue-specific genes they express. The strategic use of CTLs as effectors in cancer immunotherapy must be predicated on a more detailed understanding of their immunobiology. Although numerous studies have demonstrated that CTLs are dependent on CD4+ helper T lymphocytes for various aspects of their function, a clear picture of the underlying mechanisms has only recently become apparent. My presentation will discuss the studies that our laboratory has performed on the mechanism through which T-help is provided, and on consequences for the function and fate of CTLs of its provision or absence. The emerging picture is that T-help is provided to CTLs early during their primary activation and serves to direct cells towards a specific program of development and differentiation. Helped CTLs are endowed with the capacity for secondary expansion upon re-exposure to antigen while helpless CTLs undergo activation-induced cell death (AICD) by a TRAIL-mediated mechanism when restimulated. This is not an unavoidable fate for the helpless CTLs, however, as various cytokines can prevent their death by TRAIL through distinct mechanisms. The relevance of these findings to cancer immunotherapy will be discussed. This abstract was published in Cancer Immunity, a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer Immunology Research.
A clonogenic study of arsenic trioxide (ATO) and temozolomide (TMZ) together and in combination with radiation therapy (RT) in a human glioma cell line (2006)

11506 Background: ATO is effective in the treatment of acute promyelocytic leukemia, but its role in the management of solid tumors has yet to be defined. Post-operative therapy consisting of TMZ with and without RT is considered the standard of care for patients with newly-diagnosed glioblastoma multiforme (GBM). ATO has been shown to potentiate the effects of RT in preclinical models. Therefore, we investigated the cytotoxicity of ATO and TMZ both together and in combination with RT in the U251T human glioma cell line. Methods: U251T cells in log phase growth were treated with ATO (0.05–5 μM) and/or TMZ (0.05–5 μM) for 24 hours or sequentially according to the following schedules: ATO for 18 hours followed by TMZ for 6 hours or the reverse sequence. For RT experiments, cells were treated with 0–10 Gy of ionizing RT using a Cesium-137 source. Following drug and/or RT treatment, cells were replated onto 1.5 cm tissue culture dishes in triplicate and incubated at 37 o C for 8 to 10 days to form colonies. Colonies of more than 40 cells each were counted and the IC 50 values and combination indices (CI) were derived using Calcusyn software (Biosoft, Cambridge, UK). Each combination was repeated at least 3 times. Results: The mean single agent IC 50 for ATO, TMZ, and RT were 1.10 ± 0.28 μM, 1.88 ± 0.91 μM, and 2.62 ± 0.23 Gy, respectively. Simultaneous treatment with ATO and TMZ was slightly synergistic, while sequential treatment was either additive (TMZ→ATO) or synergistic (ATO→TMZ). Combinations of RT with ATO, TMZ or both were all synergistic, with the triple agent combination showing the greatest synergy. Conclusions: RT followed by ATO and TMZ given sequentially demonstrated striking synergy in U251T human glioma cells. A clinical trial of this combination therapy in patients with newly-diagnosed GBM is currently under development. [Table: see text] No significant financial relationships to disclose.