gebhart/patrepeval huggingface dataset:
Discovery of three loci increasing resistance to charcoal rot caused by <i>Macrophomina phaseolina</i> in octoploid strawberry (2021)

Charcoal rot caused by Macrophomina phaseolinais an increasing economic problem in annualized strawberry production systems around the world. Currently there are no effective postfumigation chemical controls for managing charcoal rot, and no information is available on the genetic architecture of resistance to M. phaseolina in strawberry (Fragaria ×ananassa). In this study, three multiparental discovery populations and two validation populations were inoculated at planting and evaluated for mortality in three consecutive growing seasons. Genome-wide SNP genotyping and pedigree-based analysis with FlexQTL™ software were performed. Two large-effect quantitative trait loci (QTL) increasing charcoal rot resistance were discovered and validated in cultivated germplasm. FaRMp1 was located on linkage group 2A in the interval 20.4to 24.9 cM, while FaRMp2 was located on linkage group 4B in the interval 41.1to 61.2 cM. Together these QTLs explained 27% and 17% of the phenotypic variance in two discovery populations consisting of elite breeding germplasm. For both QTLs, the resistant allele showed some evidence of partial dominance, but no significant interaction was detected between the two loci. As the dosage of resistant alleles increased from 0 to 4 across the two QTLs, mortality decreased regardless of the combination of alleles.A third locus, FaRMp3 on 4D, was discovered in FVC 11-58, a reconstituted F.×ananassa originating from diverse F. virginiana and F. chiloensis accessions. This locus accounted for 44% of phenotypic variation in four segregating crosses. These findings will form the basis for DNA-informed breeding for resistance to charcoal rot in cultivated strawberry.
Antipyretic Role of Endogenous Melanocortins Mediated by Central Melanocortin Receptors during Endotoxin-Induced Fever (1997)

Bacterial infection causes fever, an adaptive but potentially self-destructive response, in the host. Also activated are counterregulatory systems such as the pituitary-adrenal axis. Antipyretic roles have also been postulated for certain endogenous central neuropeptides, including the melanocortins (alpha-MSH-related peptides). To test the hypothesis that endogenous central melanocortins have antipyretic effects mediated by central melanocortin receptors (MCRs), we determined the effect of intracerebroventricular injection of a synthetic MCR antagonist, Ac-Nle4,c-[Asp5,DNal(2')7,Lys10]alpha-MSH(4-10)-NH2 (SHU-9119) in endotoxin-challenged rats. The efficacy and specificity of SHU-9119 as an MCR antagonist in the rat was first validated in vitro and in vivo. In vitro, in heterologous cells expressing either rat MC3-R or MC4-R, the major MCR subtypes expressed in brain, SHU-9119 showed no intrinsic agonism, but it inhibited alpha-MSH-induced cAMP accumulation (IC50 = 0.48 +/- 0.19 and 0.41 +/- 0.28 nM, respectively) and [125I]-[Nle4,DPhe7]-alpha-MSH binding (IC50 = 1.0 +/- 0.1 and 0.9 +/- 0.3 nM, respectively). In vivo, exogenous alpha-MSH (180 pmol) inhibited fever in rats when administered intracerebroventricularly 30 min after Escherichia coli lipopolysaccharide (LPS) (25 microg/kg, i.p.). When co-injected with alpha-MSH, SHU-9119 (168 pmol, i.c.v.) prevented the antipyretic action of exogenous alpha-MSH. In contrast, neither alpha-MSH nor SHU-9119, alone or in combination, affected body temperatures in afebrile rats. In LPS-treated rats, intracerebroventricular injection of SHU-9119 significantly increased fever, whereas intravenous injection of the same dose of SHU-9119 had no effect. Neither intracerebroventricular nor intravenous SHU-9119 significantly affected LPS-stimulated plasma ACTH or corticosterone levels. The results indicate that endogenous central melanocortins exert an antipyretic influence during fever by acting on MCRs located within the brain, independent of any modulation of the activity of the pituitary-adrenal axis.
Adaptive probabilistic branch and bound with confidence intervals for level set approximation (2013)

We present a simulation optimization algorithm called probabilistic branch and bound with confidence intervals (PBnB with CI), which is designed to approximate a level set of solutions for a user-defined quantile. PBnB with CI is developed for both deterministic and noisy problems with mixed continuous and discrete variables. The quality of the results is statistically analyzed with order statistic techniques and confidence intervals are derived. Also, the number of samples and replications are designed to achieve a certain quality of solutions. When the algorithm terminates, it provides an estimation of the desired quantile with confidence intervals, and an approximation level set, including a statistically guaranteed set in the true desirable level set, a statistically pruned set, and a set which is not statistically specified. We also present numerical experiments with benchmark functions to visualize the algorithm and its capability.
The effects of racket inertia tensor on elbow loadings and racket behavior for central and eccentric impacts. (2006)

This paper discusses the inertia tensors of tennis rackets and their influence on the elbow swing torques in a forehand motion, the loadings transmitted to the elbow from central and eccentric impacts, and the racket acceleration responses from central and eccentric impacts. Inertia tensors of various rackets with similar mass and mass center location were determined by an inertia pendulum and were found to vary considerably in all three orthogonal directions. Tennis swing mechanics and impact analyses were performed using a computer model comprised of a full-body model of a human, a parametric model of the racket, and an impact function. The swing mechanics analysis of a forehand motion determined that inertia values had a moderate linear effect on the pronation-supination elbow torques required to twist the racket, and a minor effect on the flexion-extension and valgus-varus torques. The impact analysis found that mass center inertia values had a considerable effect on the transmitted torques for both longitudinal and latitudinal eccentric impacts and significantly affected all elbow torque components. Racket acceleration responses to central and eccentric impacts were measured experimentally and found to be notably sensitive to impact location and mass center inertia values. Key PointsTennis biomechanics.Racket inertia tensor.Impact analysis.Full-body computer model.
Compact neutron source development at LBNL - eScholarship (2001)

Compact neutron source development at LBNL Jani Reijonen * , Tak Pui Lou, Bryan Tolmachoff and Ka-Ngo Leung Lawrence Berkeley National Laboratory, MS 5-121, 1 Cyclotron Road, Berkeley CA 94720, USA ABSTRACT A compact neutron generator based on D-D or D-T fusion reactions is being developed at the Lawrence Berkeley National Laboratory. The deuterium or tritium ions are produced in a radio-frequency (RF) driven multicusp plasma source. Seven beamlets are extracted and are accelerated to energy of 100 keV by means of a three-electrode electrostatic accelerator column. The ion beam then impinges on a titanium coated copper target where either the 2.4 MeV D-D or 14 MeV D-T neutrons are generated by fusion reaction. The development of the neutron tube is divided into three phases. First, the accelerator column is operated at hydrogen beam intensity of 15 mA. Second phase consists of deuterium beam runs at pulsed, low duty cycle 150 mA operation. The third phase consists of deuterium or tritium operation at 1.5 A beam current. Phase one is completed and the results of hydrogen beam testing are discussed. Low duty cycle 150 mA deuterium operation is being investigated. Neutron flux will be measured. Finally the phase three operation and the advance neutron generator designs are described. Key words: Neutron Generator, D-D Neutron Source, Multicusp Source INTRODUCTION The RF-driven multicusp ion source developed at Lawrence Berkeley National Laboratory has found numerous applications ranging from neutral beam injection systems for fusion reactors to particle accelerators, proton therapy machines and ion implantation systems. Sources such as this are simple to operate, have long lifetime, high gas efficiency and provide high- density plasmas with high yield of monatomic species. These characteristics make the RF driven multicusp source a viable candidate for compact, high-output, neutron generators, utilizing the D-D or D-T fusion reactions. The cross-section of the reaction favors the D-T reaction, giving approximately two orders of magnitude higher neutron yields. See figure 1 for D-T and D-D neutron production cross-sections. Figure 1. Fusion reaction cross-sections for D-D of D-T reactions jreijonen@lbl.gov; phone 1 510 486 5240, fax 1 510 486 5105
Integrated Lithium Niobate Intensity Modulator on a Silicon Handle With Slow-Wave Electrodes (2022)

Segmented, or slow-wave electrodes have emerged as an index-matching solution to improve bandwidth of traveling-wave Mach Zehnder (MZM) and phase modulators on the thin-film lithium niobate on insulator platform. However, these devices require the use of a quartz handle or substrate removal, adding cost and additional processing. In this work, a high-speed dual-output electro-optic intensity modulator in the thin-film silicon nitride and lithium niobate material system that uses segmented electrodes for RF and optical index matching is presented. The device uses a silicon handle and does not require substrate removal. A silicon handle allows the use of larger wafer sizes to increase yield, and lends itself to processing in established silicon foundries that may not have the capability to process a quartz or fused silica wafer. The balanced MZM has an interaction region of 10 mm, shows a DC half wave voltage of 3.75 V with a 92 mW <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\text{P}\pi $ </tex-math></inline-formula> , an ultra-high extinction ratio of roughly 45 dB consistent with previous work, and a fiber-to-fiber insertion loss of 7.47 dB with a 95 GHz 3 dB bandwidth.
Nanobody repertoire generated against the spike protein of ancestral SARS-CoV-2 remains efficacious against the rapidly evolving virus (2023)

To date, all major modes of monoclonal antibody therapy targeting SARS-CoV-2 have lost significant efficacy against the latest circulating variants. As SARS-CoV-2 omicron sublineages account for over 90% of COVID-19 infections, evasion of immune responses generated by vaccination or exposure to previous variants poses a significant challenge. A compelling new therapeutic strategy against SARS-CoV-2 is that of single domain antibodies, termed nanobodies, which address certain limitations of monoclonal antibodies. Here we demonstrate that our high-affinity nanobody repertoire, generated against wild-type SARS-CoV-2 spike protein (Mast, Fridy et al. 2021), remains effective against variants of concern, including omicron BA.4/BA.5; a subset is predicted to counter resistance in emerging XBB and BQ.1.1 sublineages. Furthermore, we reveal the synergistic potential of nanobody cocktails in neutralizing emerging variants. Our study highlights the power of nanobody technology as a versatile therapeutic and diagnostic tool to combat rapidly evolving infectious diseases such as SARS-CoV-2.
Engineered Proteins Pull Double Duty (2010)

Myriad bi-specific proteins have been developed that recognize two different clinical targets, with the goal of achieving enhanced therapeutic effects as compared with proteins that interact with only one target. These engineered proteins are starting to enter clinical testing for a variety of biomedical applications, particularly cancer treatment.
Què passaria si l’energia solar fos realment barata? Un experiment mental en el "problema del canvi ambiental" (2016)

Unidad de excelencia María de Maeztu MdM-2015-0552
The ELLIPSO (tm) system: Elliptical low orbits for mobile communications and other optimum system elements (1991)

On 5 Nov. 1990, Ellipsat filed with the FCC the first application to provide voice communication services via low earth orbiting (LEO) satellites. The proposed system, ELLIPSO, aims at achieving end-user costs comparable to those in the cellular industry. On 3 Jun. 1991 Ellipsat filed for the second complement of its system. Ellipsat was also the first company to propose combined position determination and mobile voice services via low-earth orbiting satellites. Ellipsat is still the only proponent of elliptical orbits for any commercial system in the United States. ELLIPSO uses a spectrum efficient combination of FDMA and CDMA techniques. Ellipsat's strategy is to tailor required capacity to user demand, reduce initial system costs and investment risks, and allow the provision of services at affordable end-user prices. ELLIPSO offers optimum features in all the components of its system, elliptical orbits, small satellites, integrated protocol and signalling system, integrated end-user electronics, novel marketing approach based on the cooperation with the tenets of mobile communications, end-user costs that are affordable, and a low risk approach as deployment is tailored to the growth of its customer base. The efficient design of the ELLIPSO constellation and system allows estimated end-user costs in the $.50 per minute range, five to six times less than any other system of comparable capability.
Physical basis for the adaptive flexibility of <i>Bacillus</i> spore coats (2012)

Bacillus spores are highly resistant dormant cells formed in response to starvation. The spore is surrounded by a structurally complex protein shell, the coat, which protects the genetic material. In spite of its dormancy, once nutrient is available (or an appropriate physical stimulus is provided) the spore is able to resume metabolic activity and return to vegetative growth, a process requiring the coat to be shed. Spores dynamically expand and contract in response to humidity, demanding that the coat be flexible. Despite the coat's critical biological functions, essentially nothing is known about the design principles that allow the coat to be tough but also flexible and, when metabolic activity resumes, to be efficiently shed. Here, we investigated the hypothesis that these apparently incompatible characteristics derive from an adaptive mechanical response of the coat. We generated a mechanical model predicting the emergence and dynamics of the folding patterns uniformly seen in Bacillus spore coats. According to this model, spores carefully harness mechanical instabilities to fold into a wrinkled pattern during sporulation. Owing to the inherent nonlinearity in their formation, these wrinkles persist during dormancy and allow the spore to accommodate changes in volume without compromising structural and biochemical integrity. This characteristic of the spore and its coat may inspire design of adaptive materials.
Synthetic Soluble Analogs of Galactosylceramide (GalCer) Bind to the V3 Domain of HIV-1 gp120 and Inhibit HIV-1-induced Fusion and Entry (1997)

Galactosylceramide (GalCer) is an alternative receptor allowing human immunodeficiency virus (HIV)-1 entry into CD4-negative cells of neural and colonic origin. Several lines of evidence suggest that this glycosphingolipid recognizes the V3 region of HIV-1 surface envelope glycoprotein gp120. Since the V3 loop plays a key role in the fusion process driven by HIV-1, we decided to synthesize soluble analogs of GalCer with the aim to develop a new class of anti-HIV-1 agents that could neutralize HIV-1 infection through masking of the V3 loop. We describe a short route, in three steps, for the synthesis of soluble analogs of GalCer, using unprotected lactose as the starting sugar. The analogs were prescreened in an assay based on the interaction between a V3 loop-derived synthetic peptide and [3H]suramin, a polysulfonyl compound displaying high affinity for the V3 loop. One of the soluble analogs, i.e. CA52(n15), strongly inhibited the binding of [3H]suramin to the V3 peptide, with an IC50 of 1.2 microM. This molecule was also able to inhibit [3H]suramin binding to recombinant gp120 with similar activity. Using a competition enzyme-linked immunosorbent assay with highly specific anti-gp120 monoclonal antibodies, the region recognized by CA52(n15) could be mapped to amino acids 318-323, which corresponds to the highly conserved consensus motif GPGRAF. Interestingly, the region recognized by suramin, i.e. IQRGP-R-F, was partially overlapping this motif. CA52(n15) was able to inhibit HIV-1-induced cell fusion as well as HIV-1 entry into both CD4(+) and CD4(-)/GalCer+ cells. A structure-activity relationship study showed that: (i) the antiviral activity of soluble analogs of GalCer correlates with V3 loop binding, and (ii) the hydrophobic moiety of the molecule plays an important role in this activity. Taken together, these data show that synthetic analogs of GalCer can inhibit HIV-1 entry into both CD4(-) and CD4(+) cells through masking of the V3 loop.
The Regional Salmon Outmigration Study--survival and migration routing of juvenile Chinook salmon in the Sacramento-San Joaquin River Delta during the winter of 2008-09 (2013)

Juvenile Chinook salmon (Oncorhynchus tshawytscha) emigrating from natal tributaries of the Sacramento River may use a number of migration routes to navigate the Sacramento-San Joaquin River Delta (hereafter called "the Delta"), each of which may influence their probability of surviving. We applied a mark-recapture model to data from acoustically tagged juvenile late fall-run Chinook salmon that migrated through the Delta during the winter of 2008–09 to estimate route entrainment, survival, and migration times through the Delta. A tag-life study was conducted to determine the potential for premature tag failure. Tag failure began after 12 days and continued until the 45th day. Travel times of tagged fish exceeded minimum tag-failure times, indicating that survival estimates obtained from this study were negatively biased due to tag failure prior to fish exiting the Delta. Survival estimates were not adjusted and represent the joint probability of tag survival and fish survival. However, relative comparisons of survival among Chinook salmon choosing different routes appeared to be robust to tag failure, and migration-routing parameters were unaffected by tag failure. Migration-routing patterns were consistent among release groups. The Sacramento River was the primary migration route for all release groups except one. The percentage of fish entering the Sacramento River ranged from 33 to 55 percent. Sutter and Steamboat Sloughs were the secondary migration route for 9 of the 10 releases. The percentage of fish migrating through this route ranged from 10 to 35 percent. Entrainment into the interior Delta ranged from 15 to 33 percent. The Delta Cross Channel gates were open for 7 of the 10 releases. Entrainment into the interior Delta through the cross channel ranged from 1 to 27 percent. We estimated route-specific survival for 10 release groups that were released between November 14, 2008, and January 19, 2009. Population-level survival through the Delta (SDelta) ranged from 0.019 (standard error of 0.012) to 0.277 (standard error of 0.041) among releases, which represent the probability of a fish surviving from Sacramento to Chipps Island with an operational transmitter. Sacramento River flows throughout the study period were approximately 8,000–15,000 cubic feet per second at Freeport, suggesting that variability in flow contributed little to differences in survival between releases. Fish migrating through the Sacramento River had the highest survival for most releases. Survival in Sutter and Steamboat Sloughs was slightly lower than survival in the Sacramento River for 7 of the 10 releases, but higher than survival in the Sacramento River for 3 releases. Survival in the interior Delta was lowest for all release groups except for one release in November. With the exception of this November release, survival patterns across release groups were similar to those of previous studies.
EasyModeller: A graphical interface to MODELLER (2010)

EasyModeller provides a graphical straight forward interface and functions as a stand-alone tool which can be used in a standard personal computer with Microsoft Windows as the operating system.
Dual Utilization of Medicinal and Aromatic Crops as Bioenergy Feedstocks (2018)

Dual production of biofuels and chemicals can increase the economic value of lignocellulosic bioenergy feedstocks. We compared the bioenergy potential of several essential oil (EO) crops with switchgrass ( Panicum virgatum L.), a crop chosen to benchmark biomass and lignocellulosic biofuel production. The EO crops of interest were peppermint ( Mentha × piperita L.), "Scotch" spearmint ( Mentha × gracilis Sole), Japanese cornmint ( Mentha canadensis L.), and sweet sagewort ( Artemisia annua L.). We also assessed each crop for EO production in a marginal production environment in Wyoming, USA, with irrigation and nitrogen (N) rates using a split-plot experimental design. Oil content ranged from 0.31 to 0.4% for Japanese cornmint, 0.23 to 0.26% for peppermint, 0.38 to 0.5% for spearmint, and the overall mean of sweet sagewort was 0.34%. Oil yields ranged from (in kg ha<sup>-1</sup>) 34 to 165 in Japanese cornmint, 25 to 108 in peppermint, 29.3 to 126 in spearmint, and 39.7 in sweet sagewort. EO production, but not composition, was sensitive to N fertilization. The alternative bioenergy crops and switchgrass produced similar amounts of ethanol from bench-scale simultaneous saccharification and fermentation assays. Value-added incomes from the EO proceeds were estimated to be between $1055 and $5132 ha<sup>-1</sup> from peppermint, $1309 and $5580 ha<sup>-1</sup> from spearmint, $510 and $2460 ha<sup>-1</sup> from Japanese cornmint, and $3613 ha<sup>-1</sup> from sweet sagewort under Wyoming growth conditions. The advantage of the proposed crops over traditional lignocellulosic species is the production of high-value natural products in addition to lignocellulosic biofuel production.
IRF4 downregulation improves sensitivity and endurance of CAR T cell functional capacities (2023)

Chimeric antigen receptor (CAR) modified T cells can induce complete remissions in patients with advanced hematological malignancies. Nevertheless, the efficacy is mostly transient and remains so far poor in the treatment of solid tumors. Crucial barriers to long-term CAR T cell success encompass loss of functional capacities known as "exhaustion", among others. To extend CAR T cell functionality, we reduced interferon regulatory factor 4 (IRF4) levels in CAR T cells using a one-vector system encoding a specific short-hairpin (sh) RNA along with constitutive CAR expression. At baseline, CAR T cells with downregulated IRF4 showed equal cytotoxicity and cytokine release compared to conventional CAR T cells. However, under conditions of repetitive antigen encounter, IRF4<sup>low</sup> CAR T cells displayed enhanced functionality with superior cancer cell control in the long-term compared with conventional CAR T cells. Mechanistically, the downregulation of IRF4 in CAR T cells resulted in prolonged functional capacities and upregulation of CD27. Moreover, IRF4<sup>low</sup> CAR T cells were more sensitive to cancer cells with low levels of target antigen. Overall, IRF4 downregulation capacitates CAR T cells to recognize and respond to target cells with improved sensitivity and endurance.
Engineering therapeutic proteins for immune modulation (2014)

Thesis: Ph. D., Massachusetts Institute of Technology, Department of Biological Engineering, 2014.