gebhart/patrepeval huggingface dataset:
Network-Coded Broadcast: from Canonical Networks to Random Topologies (2008)

We consider the problem of finding the minimum number of transmissions in an ad-hoc network for all-to-all broadcasting using network coding. This work generalizes previous results for canonical topologies such as the circle and the wrap around grid to the finite-sized line, and non-wrap-around grid. The latter topologies better reflect network coding in random topologies, since the dissemination of information is "directional", in a sense that information usually arrives via the neighbors on the path to its originator instead of from all possible directions. We find that while the line topology requires a higher number of transmissions compared to the circle, this is interestingly not the case for the grid. We further present simulation results on a heuristic that estimates the required minimum number of transmissions in random wireless topologies and compare it to the optimum solution, as well as previously proposed heuristics.
Mapping the Bubble Trap Feeding Eruptions of Strokkur Geyser, Iceland (2021)

&amp;lt;p&amp;gt;Geysers are characterized by regular eruptions of hot water fountains. Their internal system consists of a heat source at depth, an often complex crack system and a conduit linking it to the surface. The conduit and crack system is filled with water, steam and gases similar to a volcano. Bubble traps are sometimes and rarely mapped and alternative heat-driven models for geyser eruptions exist.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;Using a multidisciplinary, dense and close network of video cameras, seismometers, water pressure sensors and a tiltmeter we studied pool geyser Strokkur in June 2018. These multidisciplinary observations and particle-motion based tremor locations enabled us to derive a schematic cross section describing the driving mechanisms and the fluid dynamic processes within the bubble trap, crack system and conduit. We imaged a bubble trap at 23.7+-4.4 m depth, 13 to 23 m west of the conduit. We divide the eruptive cycle into eruption, refilling of the conduit, gas accumulation in the bubble trap and a trail of bubbles from the bubble trap into the conduit where they collapse at depth and have gained novel insights in understanding the gas accumulation, migration and collapse in such hot geyser systems in different phases of the eruptive cycle.&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;The dataset of this experiment can be accessed here:&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;&amp;lt;strong&amp;gt;- Eibl, E. P. S.&amp;lt;/strong&amp;gt;,&amp;amp;#160;M&amp;amp;#252;ller, D., Allahbakhshi, M., Walter, T. R., Jousset, P., Hersir, G. P., Dahm, T., (2020) ' Multidisciplinary dataset at the Strokkur Geyser, Iceland, allows to study internal processes and to image a bubble trap.' GFZ Data Services. DOI: 10.5880/GFZ.2.1.2020.007&amp;lt;/p&amp;gt;&amp;lt;p&amp;gt;- &amp;lt;strong&amp;gt;Eibl, E. P. S.&amp;lt;/strong&amp;gt;; Walter, T.; Jousset, P.; Dahm, T.; Allahbakhshi, M.; M&amp;amp;#252;ller, D.; Hersir, G.P. (2020): 1 year seismological experiment at Strokkur in 2017/18. GFZ Data Services. Other/Seismic Network. DOI:10.14470/2Y7562610816&amp;lt;/p&amp;gt;
Luminescent Biosensors for Real-Time Monitoring of Intracellular cAMP (2011)

G-protein coupled, seven-transmembrane (7-TM) receptors (GPCRs) comprise a diverse class of signaling molecules involved in cellular physiology and pathology. In recent years, intracellular biosensors have been developed to monitor changes in intracellular cAMP in real time, facilitating studies on the mechanisms of GPCR activation and desensitization in living cells. However, methods based on fluorescence can show limitations in response dynamics together with being difficult to perform. Here we present the use of genetically encoded, luminescent biosensors that allow a facile, non-lytic assay format for monitoring cAMP dynamics in living cells.
Enhanced T cell effector function upon differentiation of CD8+ and CD4+ T cells in the presence of BioE-1197 through potential off target ARK family inhibition (2022)

Abstract We sought to evaluate PAS domain containing kinase (PASK) inhibition during T cell differentiation using the previously described PASK inhibitor BioE-1197. Notably, CD8+, Th1, and Th2 T cells activated and expanded in the presence of BioE-1197 display elevated lineage specific cytokine production upon restimulation compared to control differentiated T cells, suggesting BioE-1197 may prove to be a powerful means to enhance T cell function. Curiously however, BioE-1197 mediated these effects even in PASK KO T cells suggesting its mechanism of action was independent of PASK. BLAST alignment of the PASK kinase domain revealed members of the AMPK related kinases (ARK) family as potential targets of BioE-1197. ARKs phosphorylate class IIa histone deacetylases (HDACs) in response to activation. To assess whether BioE-1197 inhibits ARK family member activity, we activated and expanded CD8+ T cells with or without BioE-1197. Control differentiated CD8s show elevated phosphorylated and total HDAC7 over time after activation. However, BioE-1197 differentiated cells do not exhibit elevated phosphorylation or total expression of HDAC7 after activation. Concurrent reduction of phosphorylation and total HDAC7 is a phenotype previously reported in cells treated with ARK family kinase inhibitors, suggesting BioE-1197 may be functioning to inhibit an ARK family member(s). Ongoing work aims to definitively demonstrate that the ability of BioE-1197 to enhance effector function is via inhibition of ARK family members and the subsequent regulation of HDAC7. Overall these studies identify BioE-1197 as a novel agent to enhance effector T cell function and suggests potential utility in tumor immunotherapy and enhancing vaccine efficacy. Supported by grants from NIH (P41EB028239-03, R01AI077610-10) and the Bloomberg-Kimmel Institute for Cancer Immunotherapy.
Recommendations for a step‐wise comparative approach to the evaluation of new screening tests for colorectal cancer (2016)

New screening tests can be evaluated efficiently by this stepwise comparative approach.
Electrical characterization of millimeter-wave interconnects on low-k and low-loss oxides for advanced 3D silicon interposers (2011)

This paper presents electrical characterization of millimeter wave interconnects on oxides to realize routing layers and through-Silicon-Vias interconnections in 3D silicon interposers. As a compromise has to be found between good RF performances and temperature compliant with 3D integration technology, a wide variety of oxide insulators are tested using coplanar waveguide transmission lines. Effects increasing microwave losses are discussed, mainly losses due to the presence of charge carriers at the silicon/oxide interface but also due to light radiation and environment.
The subunit structure and carboxy-terminal sequence of rabbit muscle aldolase. (1967)

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans the biological, physical, and social sciences.
ISG15 as a Novel Target for Tumor Immunotherapy (95.13) (2010)

Abstract Passive immunotherapy is widely used in the treatment of cancer, however, active therapeutic vaccination is achieving increased effectiveness in clinic trials and in preclinical models of cancer. Our laboratory specializes in constructing therapeutic cancer vaccines that utilize Listeria monocytogenes (Lm) as a vector to induce a strong CTL response against tumor-associated antigens (TAAs) when fused to non-hemolytic Listeriolysin O (LLO). Recently, elevated expression of ISG15, an ubiquitin-like protein, has been found in human breast cancer cell lines and clinical breast cancer. After confirming elevated expression of this potential TAA in murine breast cancer models, we constructed an Lm vaccine targeting cells with elevated expression of ISG15. Our recombinant Lm vaccine, Lm-LLO-ISG15, produces and secretes a fusion protein of LLO and ISG15 proficiently. After tumor implantation and subsequent vaccinations, Lm-LLO-ISG15 significantly slowed tumor growth and reduced metastatic lung lesions in comparison to a non-specific Lm control vaccine. In addition, prior vaccination with Lm-LLO-ISG15 offered some protection against implantable tumor challenge and reduced time to tumor progression in a mouse model for sporadic breast cancer. Further work has identified two hypothetical ISG15 H2d-restricted CD8 T cell epitopes. Additional work to determine the mechanism of Lm-LLO-ISG15 anti-tumor efficacy is being pursued.
Self-referenced quantitative phase microscopy (2012)

Self-referenced quantitative phase microscopy (SrQPM) is reported, wherein quantitative phase imaging is achieved through the interference of the sample wave with a reflected version of itself. The off-axis interference between the two beams generates a spatially modulated hologram that is analyzed to quantify the sample's amplitude and phase profile. SrQPM requires approximately one-half of the object field of view to be empty and optically flat, which serves as a reference for the other half of the field of view containing the sample.
On the security and robustness of encryption via compressed sensing (2008)

The compressed sensing (CS) paradigm unifies sensing and compression of sparse signals in a simple linear measurement step. Reconstruction of the signal from the CS measurements relies on the knowledge of the measurement matrix used for sensing. Generation of the pseudo-random sensing matrix utilizing a cryptographic key, offers a natural method for encrypting the signal during CS. This CS based encryption has the inherent advantage that encryption occurs implicitly in the sensing process - without requiring additional computation. Additionally, the robustness of recovery from compressed sensing, allows a new form of ldquorobust encryptionrdquo for multimedia data, wherein the signal is recoverable with high fidelity despite the introduction of additive noise in the encrypted data. In this paper, we examine the security and robustness of this CS based encryption method. The security implications are investigated by considering brute force and structured attacks. Robustness is characterized empirically. Our analysis and results indicate that the computational complexity of these attacks renders them infeasible in practice. In addition, the CS based encryption is found to have fair robustness against additive noise, making it a promising ldquorobust encryptionrdquo technique for multimedia.
The serine/threonine protein kinasePknI controls the growth ofMycobacterium tuberculosis upon infection (2009)

The protein kinase PknI is one of 11 functional serine/threonine protein kinases in
Mycobacterium tuberculosis. Specialized transduction was performed to create a
null mutant in the pknI gene. The resulting mutant was used to determine the role
of PknI in M. tuberculosis growth and infectivity. The pknI mutant grows better
under acidic pH and limited oxygen availability. We observed a modest increased
growth of pknI mutant within macrophages during an in vitro infection and
a hypervirulence phenotype in severe combined immunodeficiency mice. The
internal signals used to activate PknI are most likely the host-associated signals
such as low pH associated with limited oxygen availability. Thus, we have shown
that PknI plays a role in sensing the host macrophage’s environment and
translating it to slow the growth of M. tuberculosis within the infected host.
G‐protein signalling mediates differential production of toxic secondary metabolites (2000)

Filamentous fungi elaborate a complex array of secondary metabolites, including antibiotics and mycotoxins. As many of these compounds pose significant economic and health concerns, elucidation of the underlying cellular mechanisms that control their production is essential. Previous work revealed that synthesis of the carcinogenic mycotoxins sterigmatocystin (ST) and aflatoxin (AF) in Aspergillus species is negatively controlled by FadA, the alpha-subunit of a heterotrimeric G-protein. In sharp contrast, we show here that the dominant activating fadA allele, fadAG42R, stimulates transcription of a gene from the A. nidulans penicillin (PN) gene cluster and elevates penicillin production. Thus, FadA has opposite roles in regulating the biosynthesis of a potent antibiotic (PN) and a lethal mycotoxin (ST) in A. nidulans. Furthermore, expression of fadAG42R in Fusarium sporotrichioides increases trichothecene (TR) mycotoxin production and alters TR gene expression. Our findings reveal that a G-protein defines an important control point for differential expression of fungal secondary metabolites within and across fungal genera. These data provide critical evidence suggesting that targeting G-protein signal transduction pathways as a means of controlling or preventing the production of a single mycotoxin could have serious undesirable consequences with regard to the production of other secondary metabolites.
Direct Modulation of Microtubule Stability Contributes to Anthracene General Anesthesia (2013)

Recently, we identified 1-aminoanthracene as a fluorescent general anesthetic. To investigate the mechanism of action, a photoactive analogue, 1-azidoanthracene, was synthesized. Administration of 1-azidoanthracene to albino stage 40-47 tadpoles was found to immobilize animals upon near-UV irradiation of the forebrain region. The immobilization was often reversible, but it was characterized by a longer duration consistent with covalent attachment of the ligand to functionally important targets. IEF/SDS-PAGE examination of irradiated tadpole brain homogenate revealed labeled protein, identified by mass spectrometry as β-tubulin. In vitro assays with aminoanthracene-cross-linked tubulin indicated inhibition of microtubule polymerization, similar to colchicine. Tandem mass spectrometry confirmed anthracene binding near the colchicine site. Stage 40-47 tadpoles were also incubated 1 h with microtubule stabilizing agents, epothilone D or discodermolide, followed by dosing with 1-aminoanthracene. The effective concentration of 1-aminoanthracene required to immobilize the tadpoles was significantly increased in the presence of either microtubule stabilizing agent. Epothilone D similarly mitigated the effects of a clinical neurosteroid general anesthetic, allopregnanolone, believed to occupy the colchicine site in tubulin. We conclude that neuronal microtubules are "on-pathway" targets for anthracene general anesthetics and may also represent functional targets for some neurosteroid general anesthetics.
Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy (2014)

The incidence of dementia is increasing at an alarming rate, and has become a major public health concern. Alzheimer disease (AD) is the most common form of dementia and is characterized by progressive cognitive impairment. In addition to classical neuropathological features such as amyloid plaques and neurofibrillary tangles (NFT), accumulation of activated immune cells has been documented in the AD brain, suggesting a contribution of neuroinflammation in the pathogenesis of AD. Besides cognitive deterioration, non-cognitive symptoms, such as agitation, aggression, depression and psychosis, are often observed in demented patients, including those with AD, and these neuropsychological symptoms place a heavy burden on caregivers. These symptoms often exhibit sudden onset and tend to fluctuate over time, and in many cases, they are triggered by an infection in peripheral organs, suggesting that inflammation plays an important role in the pathogenesis of these non-cognitive symptoms. However, there is no mechanistic explanation for the relationship between inflammation and neuropsychiatric symptoms. Observations from experimental mouse models indicate that alteration of brain blood vessels, especially blood-brain barrier (BBB) dysfunction, may contribute to the relationship. The current review summarizes the results from recent studies on the relationship between inflammation and AD, while focusing on cerebrovascular alterations, which might provide an insight into the pathogenesis of cognitive/non-cognitive symptoms in AD patients and suggest a basis for the development of new therapeutic treatments for these conditions.
Human iPSC-Derived Cardiomyocytes Are Susceptible to SARS-CoV-2 Infection (2020)

Coronavirus disease 2019 (COVID-19) is a pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). COVID-19 is defined by respiratory symptoms, but cardiac complications including viral myocarditis are also prevalent. Although ischemic and inflammatory responses caused by COVID-19 can detrimentally affect cardiac function, the direct impact of SARS-CoV-2 infection on human cardiomyocytes is not well understood. Here, we utilize human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) as a model to examine the mechanisms of cardiomyocyte-specific infection by SARS-CoV-2. Microscopy and RNA sequencing demonstrate that SARS-CoV-2 can enter hiPSC-CMs via ACE2. Viral replication and cytopathic effect induce hiPSC-CM apoptosis and cessation of beating after 72 h of infection. SARS-CoV-2 infection activates innate immune response and antiviral clearance gene pathways, while inhibiting metabolic pathways and suppressing <i>ACE2</i> expression. These studies show that SARS-CoV-2 can infect hiPSC-CMs <i>in vitro</i>, establishing a model for elucidating infection mechanisms and potentially a cardiac-specific antiviral drug screening platform.
Characterization of channel add/drop functions using donor/acceptor point defects in two dimensional photonic crystal slabs (2003)

Channel add/drop functions using donor/acceptor point defects in two dimensional photonic crystal slabs are quantitatively investigated and compared. Spectral width of donor defect is found to be much narrower than that of acceptor defect.
Direct Measurement of Interfacial Curvature Distributions in a Bicontinuous Block Copolymer Morphology (2000)

Self-consistent field theory predicts that the complex phase behavior of block copolymers does not originate solely from the interface seeking constant mean curvature as once thought, but instead reflects competing minimization of interfacial tension and packing frustration. To test this prediction, we directly measure interfacial curvature distributions from a 3D image reconstruction of the bicontinuous gyroid morphology. Results obtained here reveal that the gyroid interface is not constant mean curvature and confirm the importance of packing frustration in the stabilization of such complex nanostructures.
Supplementary Figure 1 from Complement-Dependent Tumor Cell Lysis Triggered by Combinations of Epidermal Growth Factor Receptor Antibodies (2023)

Supplementary Figure 1 from Complement-Dependent Tumor Cell Lysis Triggered by Combinations of Epidermal Growth Factor Receptor Antibodies
Catalytic asymmetric synthesis of cyclopropylphosphonates Catalysts' scope and reactivity (2005)

The transition metal-catalyzed cyclopropanation of alkenes using α-diazomethylphosphonates leads to cyclopropylphosphonate derivatives in high yields. The reaction proceeds well with copper, rhodium, and ruthenium catalysts. The best catalysts for the enantioselective version are either Evans' Cu·bis(oxazoline) or Nishiyama's Ru·pybox.Key words: cyclopropylphosphonic acids, copper catalysts, ruthenium catalysts, cyclopropanation, diazo reagents.
A multicenter phase II, open-label trial of multiple doses of cancer vaccine candidate IGN101 to evaluate efficacy against disseminated tumor cells in blood (2005)

2557 Background: IGN101 is a vaccine designed for therapeutic immunization against cancers of epithelial origin. It consists of 0.5 mg alum-adsorbed murine monoclonal antibody 17-1A as vaccine antigen to trigger an immune response which has been shown in a phase I study with 18 patients to significantly reduce the number of circulating EpCAM-positive tumor cells in peripheral blood. Methods: An open-label, single treatment arm, uncontrolled study with at least 45 evaluable patients in at least four centers is being conducted. Patients are male or female, ≥18 years of age, with biopsy proven carcinoma likely to express EpCAM, with a Karnofsky Performance Score ≥70 at baseline and a life expectancy > 4 months. Vaccinations with IGN101 are given by subcutaneous injection on days 1, 15, 29 and 57. Analyses of circulating tumor cells (EpCAM-positive, cytokeratin-positive, CD45-negative) in peripheral blood are performed for screening of patients and on days 1, 29, 57 and 71 (study end) utilizing the method described by Cristofanilli et al., NEJM (2004) 351:781. Primary objective is to assess the effect of IGN101 on the number of circulating tumor cells in peripheral blood. Secondary objectives are safety and tolerability of multiple injections of IGN101 and to obtain data for several immunological parameters. Results: 16 patients have completed the study until November 2004, the median number of circulating tumor cells has been reduced from 10.5 at day 1 to 5 cells per blood sample after 4 vaccinations at day 71. This difference is not yet statistically significant. Conclusions: In a number of patients with colorectal, ovarian and breast cancer a reduction of circulating tumor cells is being observed after conclusion of approximately one third of the study. It has been shown that in metastatic breast cancer patients an elevated number of circulating tumor cells predicts short survival (Hayes et al., J. Clin. Oncol., ASCO Annual Meeting Proceedings (2004) 22: 509). This parameter could potentially be used to probe for surrogate efficacy in patients at an early stage of development of immunotherapy. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration igeneon AG igeneon igeneon AG igeneon AG
Comparison of Lymphocyte–CRP Ratio to Conventional Inflammatory Markers for Predicting Clinical Outcomes in COVID-19 (2023)

<b>Background</b>: In COVID-19 patients, lymphocyte-CRP ratio (LCR) is a promising biomarker for predicting adverse clinical outcomes. How well LCR performs compared to conventional inflammatory markers for prognosticating COVID-19 patients remains unclear, which hinders the clinical translation of this novel biomarker. <b>Methods:</b> In a cohort of COVID-19 inpatients, we characterised the clinical applicability of LCR by comparing its prognostic value against conventional inflammatory markers for predicting inpatient mortality and a composite of mortality, invasive/non-invasive ventilation and intensive care unit admissions. <b>Results:</b> Of the 413 COVID-19 patients, 100 (24%) patients suffered inpatient mortality. On Receiver Operating Characteristics analysis, LCR performed similarly to CRP for predicting mortality (AUC 0.74 vs. 0.71, <i>p</i> = 0.049) and the composite endpoint (AUC 0.76 vs. 0.76, <i>p</i> = 0.812). LCR outperformed lymphocyte counts (AUC 0.74 vs. 0.66, <i>p</i> = 0.002), platelet counts (AUC 0.74 vs. 0.61, <i>p</i> = 0.003) and white cell counts (AUC 0.74 vs. 0.54, <i>p</i> < 0.001) for predicting mortality. On Kaplan-Meier analysis, patients with a low LCR (below a 58 cut-off) had worse inpatient survival than patients with other LCR values (<i>p</i> < 0.001). <b>Conclusion</b>: LCR appears comparable to CRP, but outperformed other inflammatory markers, for prognosticating COVID-19 patients. Further studies are required to improve the diagnostic value of LCR to facilitate clinical translation.