gebhart/patrepeval huggingface dataset:
Impact of submesoscale processes on dynamics of phytoplankton filaments (2015)

Abstract In Monterey Bay, CA, during northwesterly, upwelling favorable winds, the development of a southward flowing cold jet along the entrance to the Bay is often observed. This dense cold jet separates warm waters of the anticyclonic circulation offshore from the water masses inside the Bay. Interactions between the cold jet and the offshore anticyclonic circulation generate ageostrophic secondary circulation (ASC) cells due to submesoscale processes as, for example, flow interaction with the development of surface frontogenesis and nonlinear Ekman pumping. Based on observations and modeling studies, we evaluate the impact of these submesoscale processes on the formation of chlorophyll a filaments during late spring‐earlier summer, and late summer time frames. We show that during the late summer time frame, ASC leads to the development of filaments with high values of chlorophyll a concentration along the edge of the cold jet–in contrast to the earlier summer time, when the ASC mixes phytoplankton much deeper to the area below of the euphotic depth, and chlorophyll a filaments are 3–4 times weaker.
Solder Joint Fatigue Studies Subjected to Board-level Random Vibration for Automotive Applications (2022)

In this paper, a simplified methodology is presented for the evaluation of test-to-failure board-level random vibrations using a combination of experimental and finite element modeling techniques in calculating equivalent stresses for SAC305 solder joints experiencing high- and ultra-high-cycle fatigue usually found in the emerging automotive robo-taxi industry. Some partial results that were obtained during this study allow for an investigation of the effects of a printed circuit board geometry on possible failure modes of Pb-free solder joints. These results seem to confirm the findings that have been reported previously by some researchers on the migration of a failure mode from the ductile fracture in the bulk solder to the brittle fracture of the intermetallic compound (IMC) layer due to the positive correlation between the tensile strength of the solder joint and the strain rate which may have occurred from high level of vibration and shock during the test. The generated data points were then compared to the existing S-N (stress-life) fatigue curves for the SAC305 solder joints in order to assess whether these curves can provide adequate results for the test vehicles fatigue life calculations. These preliminary results show that more work is needed in both verifying the effect of a failure mode migration in the solder joints as well as developing additional data points for S-N curve generation. This research is a continuation of the study initiated by the JEDEC JESD22 working group.
Induced Abortion and Breast Cancer Risk (2000)

Results from case-control studies suggest that induced abortion may be associated with a small increase in risk of breast cancer. While risk estimates from cohort studies have generally not observed such an association, these studies have had limited information regarding abortion and possible confounding variables. Therefore, we conducted a study among a cohort of post-menopausal women from whom detailed information regarding pregnancy outcomes as well as risk factors for breast cancer had been collected. The study sample included 37,247 Iowa Women's Health Study participants, 55-64 years of age at baseline in 1986, who reported no history of breast, or other, cancer (except non-melanoma skin cancer), and for whom information regarding pregnancy outcomes (that is, live birth, stillbirth, spontaneous abortion, ectopic pregnancy or induced abortion) was available. We used linkage with records of the State Health Registry of Iowa, part of the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program, to estimate the incidence of breast cancer among cohort members through 1995. We calculated age-adjusted relative risks and 95% confidence intervals using Cox proportional hazards regression. Only 653 women (1.8%) reported an induced abortion. The age-adjusted relative risk of breast cancer among women with prior induced abortion compared with those without was 1.1 (95% CI = 0.8-1.6). Relative risks were higher among women whose age at first abortion was less than 20 or at least 30 years, for those whose abortion took place after their first birth or who never gave birth, and for those with early termination (0-2 months). These estimates varied from 1.3-1.7, but the confidence intervals around each were wide. Since most women in this cohort were beyond their reproductive years when abortion became legal in 1973, the low prevalence of induced abortion argues for a cautious interpretation.
Cannabinoid receptors are absent in insects (2001)

The endocannabinoid system exerts an important neuromodulatory role in mammals. Knockout mice lacking cannabinoid (CB) receptors exhibit significant morbidity. The endocannabinoid system also appears to be phylogenetically ancient--it occurs in mammals, birds, amphibians, fish, sea urchins, leeches, mussels, and even the most primitive animal with a nerve network, the Hydra. The presence of CB receptors, however, has not been examined in terrestrial invertebrates (or any member of the Ecdysozoa). Surprisingly, we found no specific binding of the synthetic CB ligands [(3)H]CP55,940 and [(3)H]SR141716A in a panel of insects: Apis mellifera, Drosophila melanogaster, Gerris marginatus, Spodoptera frugiperda, and Zophobas atratus. A lack of functional CB receptors was confirmed by the inability of tetrahydrocannabinol (THC) and HU210 to activate G-proteins in insect tissues, utilizing a guanosine-5'-O-(3-[(35)]thio)-triphosphate (GTP gamma S) assay. No orthologs of human CB receptors were located in the Drosophila genome, nor did we find orthologs of fatty acid amide hydrolase. This loss of CB receptors appears to be unique in the field of comparative neurobiology. No other known mammalian neuroreceptor is understood to be missing in insects. We hypothesized that CB receptors were lost in insects because of a dearth of ligands; endogenous CB ligands are metabolites of arachidonic acid, and insects produce little or no arachidonic acid or endocannabinoid ligands, such as anandamide.
Nirmatrelvir-resistant SARS-CoV-2 is efficiently transmitted in Syrian hamsters (2022)

Abstract The SARS-CoV-2 main protease (3CLpro) is one of the promising therapeutic target for the treatment of COVID-19. Nirmatrelvir is the only the 3CLpro inhibitor authorized for treatment of COVID-19 patients at high risk of hospitalization; other 3Lpro inhibitors are in development. We recently repored on the in vitro selection of a SARS-CoV2 3CLpro (L50F-E166A-L167F; short 3CLpro res ) virus that is cross-resistant with nirmatrelvir and yet other 3CLpro inhibitors. Here, we demonstrate that the resistant virus replicates efficiently in the lungs of intranassaly infected hamsters and that it causes a lung pathology that is comparable to that caused by the WT virus. Moreover, 3CLpro res infected hamsters transmit the virus efficiently to co-housed non-infected contact hamsters. Fortunately, resistance to Nirmatrelvir does not readily develop (in the clinical setting) since the drug has a relatively high barrier to resistance. Yet, as we demonstrate, in case resistant viruses emerge, they may easily spread and impact therapeutic options for others. Therefore, the use of SARS-CoV-2 3CLpro protease inhibitors in combinations with drugs that have a different mechanism of action, may be considered to avoid the development of drug-resistant viruses in the future.
Detection of Phase Transformation in Hot Strip Steel Samples Using A Multi-Frequency Electromagnetic Impedance Measuring Node (2018)

This paper considers the development of such a multi-frequency device and an investigation into the application of detecting rolling characteristics of hot steel. The results suggest that such a device is capable of on-line measurement, although further research is required to develop the necessary algorithms.
The effect of mismatch and disturbances on the quadrature relation of a cross-coupled relaxation oscillator (2002)

Cross-coupled relaxation oscillators are capable of producing two stable and highly accurate, quadrature output signals. We present a complete high-level model of the cross-coupled relaxation oscillator in terms of circuit parameters, from which we obtain explicit expressions for duty-cycle, oscillation frequency and output phase relation. They predict the influence of mismatches and other disturbances such as delays, at circuit level. The results provide useful guidelines for the design of a high performance circuit of such an oscillator. The theoretical results are confirmed by simulation and by experiment.
Laser Writing: Direct Laser Writing of Photoresponsive Colloids for Microscale Patterning of 3D Porous Structures (Adv. Mater. 1/2009) (2009)

On pg. 66, Paul Braun and co-workers report the use of direct laser writing to pattern porous 3D structures from photo-responsive colloidal building blocks. Upon 2-photon exposure, the colloids become highly attractive, enabling localized control of aggregation behavior. 3D structures composed of porous walls are harvested by writing into a colloidal sediment of these particles, followed by rinsing away unexposed colloidal species. Applications may include microfluidics, and studies of porous media, cellular growth and signaling, and colloidal physics. Cover art by Steven Eisenmann of the Beckman Institute VMIL.
Evaluation Regarding the Efficacy and Safety of a Probiotic Mixture in Healthy Volunteers with Evacuation Disorders (2012)

Probiotics have been used in humans for almost a century and are widely recommended because they play an important role in gastrointestinal physiological and pathophysiological processes. The aim of this study was to evaluate the effi- cacy and safety of a probiotic mixture in healthy volunteers with evacuation disorders. We undertook a prospective study with historical control. We used the number of evacuations, effort and stool consistency 10 days before, 10 days during and 10 days after treatment with the probiotic as primary outcome measures. Eligible par-ticipants comprised 25 patients with an average age of 25.12 years (range: 18 - 55) who suffered from evacuation disorders. BIO L6 is a func- tional food consisting of a probiotic preparation that contains 1 mg (108 CFUs) of lyophilized strains of Lactic Acid Bacteria resuspended in 250 mL of drinking water. The probiotic preparation was prescribed daily for two weeks, five days a week. A significant increase in the number of evacuations was observed in 23 patients during BIO L6 consump- tion and continued in 20 after consumption. The degree of effort spent defecating decreased in 17 patients during treat- ment and in 7 after treatment. A significant improvement (P < 0.001) in stool consistency was also observed in all pa- tients receiving BIO L6. Fourteen patients had at least one adverse event (AE) for one or two days during treatment; most treatment-related AEs were considered minor or mild in terms of severity and were consistent with AEs reported for probiotic consumption. The results of this study suggest that the use of probiotic mixture BIO L6 is effective, safe and tolerable and provides beneficial effects for subjects with evacuations disorders.
Mycophenolic acid and methotrexate inhibit lymphocyte cytokine production via different mechanisms. (2003)

Mycophenolic acid (MPA) and methotrexate (MTX) are immunosuppressive drugs used for the treatment of various immunological disorders. MPA is an inhibitor of inosine monophosphate dehydrogenase and MTX is a folate antagonist that inhibits tetrahydrofolate reductase. Production of T cell cytokines in whole blood cultures, as well as in PBMC cultures, is inhibited by a low concentration of both drugs. Inhibition of cytokine production after monocyte stimulation was less evident. The mechanism by which inhibition is achieved is different for both drugs. Inhibition of T cell cytokine production by MPA was more profound and started earlier compared to the inhibition by MTX. MTX induced apoptosis in T cells that became activated, whereas MPA prevented activation of T cells by arresting the cell cycle in the G0/G1 phase. Addition of guanosine and adenosine can overcome this cell cycle arrest, even after several days. Furthermore MPA inhibited the expression of activation markers HLA-DR and CD71 on T cells. The observation that MTX cannot prevent T cell activation but induces apoptosis in activated T cells, and that MPA reversibly prevents activation of T cells could explain the immunosuppressive effects of both these drugs.
The PRKAA1/AMPKα1 pathway triggers autophagy during CSF1-induced human monocyte differentiation and is a potential target in CMML (2015)

Autophagy is induced during differentiation of human monocytes into macrophages that is mediated by CSF1/CSF-1/M-CSF (colony stimulating factor 1 [macrophage]). However, little is known about the molecular mechanisms that link CSF1 receptor engagement to the induction of autophagy. Here we show that the CAMKK2-PRKAA1-ULK1 pathway is required for CSF1-induced autophagy and human monocyte differentiation. We reveal that this pathway links P2RY6 to the induction of autophagy, and we decipher the signaling network that links the CSF1 receptor to P2RY6-mediated autophagy and monocyte differentiation. In addition, we show that the physiological P2RY6 ligand UDP and the specific P2RY6 agonist MRS2693 can restore normal monocyte differentiation through reinduction of autophagy in primary myeloid cells from some but not all chronic myelomonocytic leukemia (CMML) patients. Collectively, our findings highlight an essential role for PRKAA1-mediated autophagy during differentiation of human monocytes and pave the way for future therapeutic interventions for CMML.
Mapping the Specificity of SH3 Domains with Phage-Displayed Random-Peptide Libraries (2003)

Recent inqui-res into the molecular mechanisms underlying cellular behavior have underscored the importance of dynamic associations between proteins, or protein-protein interactions, in regulating a variety of brological processes. These protein-protein interactions are often mediated by conserved-modular domains, such as the Src Homology domains 2 and 3, known as SH2 and SH3 (1,2). Recently, combmatorral-peptrde libraries have been used to define high-affinity peptide ligands for a variety of modular domains (3–8). Ligands derived from these libraries often resemble sequences in natural-binding proteins. Thus, combinatorral-peptide libraries provide a means of mapping modular domain-mediated protein-protein interactions, particularly where the natural target of the domain is a short linear stretch of ammo acids.
Neuronal T-Cell Autoreactivity Is Amplified in Overweight Children With New-Onset Insulin-Requiring Diabetes (2014)

Our observations link obesity and diabetes-related autoimmunity, suggesting an amplification of neuronal T-cell autoimmunity associated with adiposity and/or insulin resistance, with obesity-related inflammation possibly enhancing islet autoimmunity.
2185 The effects of autoimmune inflammation on proliferation, differentiation, and androgen receptor signaling in adult prostate stem cells (2018)

OBJECTIVES/SPECIFIC AIMS: The primary goal of this project is to verify findings from a murine prostatitis model in the human setting. METHODS/STUDY POPULATION: Methods include primary cell isolation and culture, FACS, adoptive transfer, 3D cell culture, histology, immunofluorescence, xenograft, and tissue recombination. The study population includes patients undergoing HoLEP or radical prostatectomy due to hyperplasia or adjacent bladder or prostate cancer. RESULTS/ANTICIPATED RESULTS: Having verified similar sensitivities to androgen receptor (AR) inhibitors between naive murine and human basal prostate stem cells, we anticipate that autoimmune inflammation in humans affects the response of basal prostate stem cells in a manner similar to the murine setting as well. This includes increased proliferation, increased differentiation, and decreased response to AR inhibitors. DISCUSSION/SIGNIFICANCE OF IMPACT: The identification of survival mechanisms used by basal prostate stem cells in an androgen deprived environment may give insight to the process by which prostate cancer becomes androgen independent. The effect of inflammation on proliferation, survival, and AR signaling in these cells may also provide information relevant to cancer initiation and progression.
Hadron properties in lattice QCD with dynamical fermions (1989)

Incorporating dynamical Kogut-Susskind fermions into a Monte Carlo simulation of QCD, we have analyzed the masses of low-lying hadrons, chiral-symmetry breaking, and the interquark potential. We used a 24\ifmmode\times\else\texttimes\fi{}${12}^{3}$ lattice for two couplings $g$, where $\ensuremath{\beta}=\frac{6}{{g}^{2}}=5.20 \mathrm{and} 5.35$. The quark masses were $ma=0.075, 0.050, \mathrm{and} 0.025$ ($a$ being the lattice spacing). We find that the pattern of hadron masses of the $\ensuremath{\pi}$, $\ensuremath{\rho}$, and $N$ is qualitatively as seen experimentally. The pion mass squared is proportional to the quark mass and thus behaves as expected from chiral symmetry. Values for the quark condensate extrapolated to $ma=0$, the renormalization-group-invariant quark mass, and the pion decay constant are in reasonable agreement with values derived from experiment or from current algebra. If we fix the lattice spacing from the $\ensuremath{\rho}$ mass, we see evidence for the screening effect of light-quark-antiquark pairs in the potential between two massive quarks. At $\ensuremath{\beta}=5.20$ and $ma=0.050$ we find good agreement between the results from our pseudofermion method and those from a hybrid simulation.
An objective method for combining multi‐parametric MRI datasets to characterize malignant tumors (2007)

Medical imaging has made significant contributions to the characterization of malignant tumors. In many cases, however, maps from multiple modalities may be required for more complete tumor mapping. In this manuscript we propose an objective method for combining multiple imaging datasets with the goal of characterizing malignant tumors. We refer to the proposed technique as the percent overlap method (POM). To demonstrate the power and flexibility of the POM analysis, we present four patients with recurrent glioblastoma multiforme. Each patient had multiple magnetic resonance imaging procedures resulting in seven different parameter maps. Chemical shift imaging was used to provide three metabolite ratio maps (Cho:NAA, Cho:Cre, Lac:Cre). A perfusion scan provided regional cerebral blood volume and permeability maps. Diffusion and carbogen-based hypoxia mapping data were also acquired. Composite maps were formed for each patient using POM, then were compared to results from the ISODATA clustering technique. The POM maps of likely recurrent tumor regions were found to be consistent with the ISODATA clustering method. This manuscript presents an objective method for combining parameters from multiple physiologic imaging techniques into a single composite map. The accuracy of the map depends strongly on the sensitivity of the chosen imaging parameters to the disease process at the time of image acquisition. Further validation of this method may be achieved by correlation with histological data.
Diverse <scp>NLR</scp> immune receptors activate defence via the <scp>RPW</scp>8‐<scp>NLR NRG</scp>1 (2018)

Most land plant genomes carry genes that encode RPW8-NLR Resistance (R) proteins. Angiosperms carry two RPW8-NLR subclasses: ADR1 and NRG1. ADR1s act as 'helper' NLRs for multiple TIR- and CC-NLR R proteins in Arabidopsis. In angiosperm families, NRG1 co-occurs with TIR-NLR Resistance (R) genes. We tested whether NRG1 is required for signalling of multiple TIR-NLRs. Using CRISPR mutagenesis, we obtained an nrg1a-nrg1b double mutant in two Arabidopsis accessions, and an nrg1 mutant in Nicotiana benthamiana. These mutants are compromised in signalling of all TIR-NLRs tested, including WRR4A, WRR4B, RPP1, RPP2, RPP4 and the pairs RRS1/RPS4, RRS1B/RPS4B, CHS1/SOC3 and CHS3/CSA1. In Arabidopsis, NRG1 is required for the hypersensitive cell death response (HR) and full oomycete resistance, but not for salicylic acid induction or bacterial resistance. By contrast, nrg1 loss of function does not compromise the CC-NLR R proteins RPS5 and MLA. RPM1 and RPS2 (CC-NLRs) function is slightly compromised in an nrg1 mutant. Thus, NRG1 is required for full TIR-NLR function and contributes to the signalling of some CC-NLRs. Some NRG1-dependent R proteins also signal partially via the NRG1 sister clade, ADR1. We propose that some NLRs signal via NRG1 only, some via ADR1 only and some via both or neither.
A quantitative method for the detection of spliced X-box binding protein-1 (XBP1) mRNA in primary bronchial epithelial cells (PBEC) as a measure of endoplasmatic reticulum (ER) stress (2011)

Accumulation of unfolded or misfolded proteins in the ER can cause ER stress, which is increasingly seen in diseases such as cystic fibrosis, alpha-1 antitrypsin deficiency and Alzheimer disease. ER stress leads to the activation of the unfolded protein response (UPR). UPR signaling involves splicing of XBP1 mRNA and leads to the induction of the chaperone protein BiP and the transcription factor CHOP, which is a key-signaling component of ER-stress induced apoptosis. In present studies, XBP1 splicing is frequently used as an important marker for ER-stress and is visualized by gel electrophoresis which is laborious and difficult to quantify. The aim of this study was to develop and validate a quantitative RT-PCR (qPCR) which detects only the spliced form of XBP1 mRNA. We stimulated PBEC with thapsigargin and tunicamycin, both known ER-stress inducers, and performed a qPCR with primers that were designed to recognize only the spliced form of XBP1. We also performed qPCR for CHOP and BiP and correlated this with the spliced XBP1 mRNA to validate the results. The spliced XBP1 PCR product was also confirmed by DNA sequencing. The correlation of XBP1 splicing with the induction of CHOP and BiP was r=0.962 (p&lt;0.000) and r=0.884 (p&lt;0.000), respectively. We compared the new method with the visualization of the spliced XBP1 mRNA by gel electrophoresis and we obtained similar results. In conclusion, we have developed a simple and quantitative method for the detection of spliced XBP1 mRNA. This study was supported in part by a grant from the Netherlands Asthma Foundation.