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At least 127 records · Page 7

Spectral Threshold for Extremal Cyclic Edge-Connectivity

In this report, the cyclic edge-connectivity of a graph G is the least k such that there exists a set of k edges whose removal disconnects G into components where every component contains a cycle. We show that for graphs of minimum degree at least 3 and girth g at least 4, the cyclic edge-connectivity is bounded above by (Δ-2)g where Δ is the maximum degree. We then prove that if the second eigenvalue of the adjacency matrix of a d-regular graph of girth g ≥ 4 is sufficiently small, then the cyclic edge-connectivity is (d-2)g, providing a spectral condition for when this upper bound on cyclic edge-connectivity is tight.

97 MATHEMATICS AND COMPUTING↗

Engineering well-expressed, V2-immunofocusing HIV-1 envelope glycoprotein membrane trimers for use in heterologous prime-boost vaccine regimens

HIV-1 vaccine immunofocusing strategies may be able to induce broadly-reactive neutralizing antibodies (NAbs). Here, we engineered a panel of diverse, membrane-resident native HIV-1 trimers vulnerable to two broad targets—the V2 apex and fusion peptide (FP). Selection criteria included i) high expression and ii) infectious function, so that trimer neutralization sensitivity can be profiled in pseudovirus (PV) assays. Initially, we boosted the expression of 17 candidate trimers by truncating gp41 and introducing a gp120-gp41 SOS disulfide to prevent gp120 shedding. "Repairs" were made to fill glycan holes and eliminate other strain-specific aberrations. A new neutralization assay allowed PV infection when our standard assay was insufficient. Trimers with exposed V3 loops, a target of non-NAbs, were discarded. To try to increase V2-sensitivity, we removed clashing glycans and modified the C-strand. Notably, a D167N mutation improved V2-sensitivity in several cases. Glycopeptide analysis of JR-FL trimers revealed near complete sequon occupation and that filling the N197 glycan hole was well-tolerated. In contrast, sequon optimization and inserting/removing glycans at other positions frequently had global "ripple" effects on glycan maturation and sequon occupation throughout the gp120 outer domain and gp41. V2 MAb CH01 selectively bound to trimers with small high mannose glycans near the base of the V1 loop, thereby avoiding clashes. Knocking in a rare N49 glycan was found to perturb gp41 glycans, increasing FP NAb sensitivity—and sometimes improving expression. Finally, a biophysical analysis of VLPs revealed that i) ~25% of particles bear Env spikes, ii) spontaneous particle budding is high and only increases 4-fold upon Gag transfection, and iii) Env+ particles express ~30–40 spikes. Taken together, we identified 7 diverse trimers with a range of sensitivities to two targets to allow rigorous testing of immunofocusing vaccine concepts.

60 APPLIED LIFE SCIENCES↗

Robust adaptive kinematic control of redundant robots

The paper presents a general method for the resolution of redundancy that combines the Jacobian pseudoinverse and augmentation approaches. A direct adaptive control scheme is developed to generate joint angle trajectories for achieving desired end-effector motion as well as additional user defined tasks. The scheme ensures arbitrarily small errors between the desired and the actual motion of the manipulator. Explicit bounds on the errors are established that are directly related to the mismatch between actual and estimated pseudoinverse Jacobian matrix, motion velocity and the controller gain. It is shown that the scheme is tolerant of the mismatch and consequently only infrequent pseudoinverse computations are needed during a typical robot motion. As a result, the scheme is computationally fast, and can be implemented for real-time control of redundant robots. A method is incorporated to cope with the robot singularities allowing the manipulator to get very close or even pass through a singularity while maintaining a good tracking performance and acceptable joint velocities. Computer simulations and experimental results are provided in support of the theoretical developments.

Tarokh, M.↗

Robot Position Sensor Fault Tolerance

Robot systems in critical applications, such as those in space and nuclear environments, must be able to operate during component failure to complete important tasks. One failure mode that has received little attention is the failure of joint position sensors. Current fault tolerant designs require the addition of directly redundant position sensors which can affect joint design. A new method is proposed that utilizes analytical redundancy to allow for continued operation during joint position sensor failure. Joint torque sensors are used with a virtual passive torque controller to make the robot joint stable without position feedback and improve position tracking performance in the presence of unknown link dynamics and end-effector loading. Two Cartesian accelerometer based methods are proposed to determine the position of the joint. The joint specific position determination method utilizes two triaxial accelerometers attached to the link driven by the joint with the failed position sensor. The joint specific method is not computationally complex and the position error is bounded. The system wide position determination method utilizes accelerometers distributed on different robot links and the end-effector to determine the position of sets of multiple joints. The system wide method requires fewer accelerometers than the joint specific method to make all joint position sensors fault tolerant but is more computationally complex and has lower convergence properties. Experiments were conducted on a laboratory manipulator. Both position determination methods were shown to track the actual position satisfactorily. A controller using the position determination methods and the virtual passive torque controller was able to servo the joints to a desired position during position sensor failure.

Aldridge, Hal A.↗

Catalyst for Carbon Monoxide Oxidation

In many applications, it is highly desirable to operate a CO2 laser in a sealed condition, for in an open system the laser requires a continuous flow of laser gas to remove the dissociation products that occur in the discharge zone of the laser, in order to maintain a stable power output. This adds to the operating cost of the laser, and in airborne or space applications, it also adds to the weight penalty of the laser. In a sealed CO2 laser, a small amount of CO2 gas is decomposed in the electrical discharge zone into corresponding quantities of CO and O2. As the laser continues to operate, the concentration of CO2 decreases, while the concentrations of CO and O2 correspondingly increase. The increasing concentration of O2 reduces laser power, because O2 scavenges electrons in the electrical discharge, thereby causing arcing in the electric discharge and a loss of the energetic electrons required to boost CO2 molecules to lasing energy levels. As a result, laser power decreases rapidly. The primary object of this invention is to provide a catalyst that, by composition of matter alone, contains chemisorbed water within and upon its structure. Such bound moisture renders the catalyst highly active and very long-lived, such that only a small quantity of it needs to be used with a CO2 laser under ambient operating conditions. This object is achieved by a catalyst that consists essentially of about 1 to 40 percent by weight of one or more platinum group metals (Pt, Pd, Rh, Ir, Ru, Os, Pt being preferred); about 1 to 90 percent by weight of one or more oxides of reducible metals having multiple valence states (such as Sn, Ti, Mn, Cu, and Ce, with SnO2 being preferred); and about 1 to 90 percent by weight of a compound that can bind water to its structure (such as silica gel, calcium chloride, magnesium sulfate, hydrated alumina, and magnesium perchlorate, with silica gel being preferred). Especially beneficial results are obtained when platinum is present in the catalyst composition in an amount of about 5 to 25 (especially 7) percent by weight, SnO2 is present in an amount of about 30 to 40 (especially 40) percent by weight, and silica gel is present in an amount of 45 to 55 (especially 50) percent by weight. The composition of this catalyst was suggested by preliminary experiments in which a Pt/SnO2 catalyst was needed for bound water to enhance its activity. These experimental results suggested that if the water were bound to the surface, this water would enhance and prolong catalyst activity for long time periods. Because the catalyst is to be exposed to a laser gas mixture, and because a CO2 laser can tolerate only a very small amount of moisture, a hygroscopic support for the catalyst would provide the needed H2O into the gas. Silica gel is considered to be superior because of its property to chemisorb water on its surface over a wide range of moisture content.

Davis, Patricia↗

A multi-pronged evaluation of aldehyde-based tripeptidyl main protease inhibitors as SARS-CoV-2 antivirals

As an essential enzyme of SARS-CoV-2, the COVID-19 pathogen, main protease (M Pro ) is a viable target to develop antivirals for the treatment of COVID-19. By varying chemical compositions at both P2 and P3 positions and the N-terminal protection group, we synthesized 18 tripeptidyl M Pro inhibitors that contained also an aldehyde warhead and β-(S-2-oxopyrrolidin-3-yl)-alaninal at the P1 position. Systematic characterizations of these inhibitors were conducted, including their in vitro enzymatic inhibition potency, X-ray crystal structures of their complexes with M Pro , their inhibition of M Pro transiently expressed in 293T cells, and cellular toxicity and SARS-CoV-2 antiviral potency of selected inhibitors. These inhibitors have a large variation of determined in vitro enzymatic inhibition IC 50 values that range from 4.8 to 650 nM. Here, the determined in vitro enzymatic inhibition IC 50 values reveal that relatively small side chains at both P2 and P3 positions are favorable for achieving high in vitro M Pro inhibition potency, the P3 position is tolerable toward unnatural amino acids with two alkyl substituents on the α-carbon, and the inhibition potency is sensitive toward the N-terminal protection group. X-ray crystal structures of M Pro bound with 16 inhibitors were determined. In all structures, the M Pro active site cysteine interacts covalently with the aldehyde warhead of the bound inhibitor to form a hemithioacetal that takes an S configuration. For all inhibitors, election density around the N-terminal protection group is weak indicating possible flexible binding of this group to M Pro . In M Pro , large structural variations were observed on residues N142 and Q189. Unlike their high in vitro enzymatic inhibition potency, most inhibitors showed low potency to inhibit M Pro that was transiently expressed in 293T cells. Inhibitors that showed high potency to inhibit M Pro transiently expressed in 293T cells all contain O-tert-butyl-threonine at the P3 position. These inhibitors also exhibited relatively low cytotoxicity and high antiviral potency. Overall, our current and previous studies indicate that O-tert-butyl-threonine at the P3 site is a key component to achieve high cellular and antiviral potency for tripeptidyl aldehyde inhibitors of M Pro .

60 APPLIED LIFE SCIENCES↗

Data for Optimizing Chemical-Free Pretreatment for Maximizing Oil/Lipid Recovery from Transgenic Bioenergy Crops and its Rapid Analysis Using Time Domain-NMR

Transgenic bioenergy crops have shown the potential to produce vegetative oil by accumulating energy-rich triacylglyceride molecules that can be converted into biofuels (biodiesel and biojet). These transgenic crops cater to improved biofuel yield by providing lipids along with cellulosic sugars. Efficient bioprocessing technologies are needed to utilize these transgenic plants to their maximum potential. To this end, this study investigates a low- and high-severity chemical-free hydrothermal pretreatment of transgenic oilcane 1566 bagasse with in situ lipids to maximize the recovery of lipids for biodiesel and fermentable sugars for ethanol with minimal inhibitor generation. Hydrothermal pretreatment at 170°C recovered ∼25% of total lipids in the pretreatment liquor, leaving the remainder in bagasse residue for hexane recovery post fermentation. The recovery of lipids in pretreatment liquor remained constant beyond 170°C. Along with lipids, ∼35% w/w and ∼50% w/w fermentable sugars were recovered post saccharification from bagasse pretreated at 170°C and 210°C for 20 min, respectively. Hydrothermal pretreatment at 170°C for 20 min provided the optimum conditions for maximum recovery of lipids and cellulosic sugars that resulted in enhanced biofuel yield per unit biomass. High severity pretreatment increased the generation of inhibitors beyond the tolerance of fermentation microorganisms. In addition, the application of time-domain proton NMR spectroscopy was extended to bioprocessing. NMR technology facilitated the analysis of total lipids, the composition of fatty acids, and the characterization of free and bound lipids in untreated and pretreated oilcane 1566 bagasse subsequent to each step of biomass to biofuel conversion.

Conversion↗

Theoretical consistency test of steam transport properties

The kinetic theory of polyatomic gases is used to test the mutual consistency of the thermal conductivity, viscosity, and specific heat of low-pressure steam from 100 to 700 C. No inconsistency exists within the cited tolerances of the skeleton tables recommended by the Sixth International Conference on the Properties of Steam, but there is some basis for suspecting that the high-temperature thermal conductivity values are slightly low. Methods for tightening the consistency bounds are suggested.

Thoen-Hellemans, J.↗

A selective WDR5 degrader inhibits acute myeloid leukemia in patient-derived mouse models

Interactions between WD40 repeat domain protein 5 (WDR5) and its various partners such as mixed lineage leukemia (MLL) and c-MYC are essential for sustaining oncogenesis in human cancers. However, inhibitors that block protein-protein interactions (PPIs) between WDR5 and its binding partners exhibit modest cancer cell killing effects and lack in vivo efficacy. Here, we present pharmacological degradation of WDR5 as a promising therapeutic strategy for treating WDR5-dependent tumors and report two high-resolution crystal structures of WDR5-degrader-E3 ligase ternary complexes. We identified an effective WDR5 degrader via structure-based design and demonstrated its in vitro and in vivo antitumor activities. On the basis of the crystal structure of an initial WDR5 degrader in complex with WDR5 and the E3 ligase von Hippel–Lindau (VHL), we designed a WDR5 degrader, MS67, and demonstrated the high cooperativity of MS67 binding to WDR5 and VHL by another ternary complex structure and biophysical characterization. MS67 potently and selectively depleted WDR5 and was more effective than WDR5 PPI inhibitors in suppressing transcription of WDR5-regulated genes, decreasing the chromatin-bound fraction of MLL complex components and c-MYC, and inhibiting the proliferation of cancer cells. In addition, MS67 suppressed malignant growth of MLL-rearranged acute myeloid leukemia patient cells in vitro and in vivo and was well tolerated in vivo. Collectively, our results demonstrate that structure-based design can be an effective strategy to identify highly active degraders and suggest that pharmacological degradation of WDR5 might be a promising treatment for WDR5-dependent cancers.

99 GENERAL AND MISCELLANEOUS↗

The Effects of Impactor Shape on the Compression After Impact Strength of Carbon/Epoxy Face Sheet Aluminum Honeycomb Core Sandwich Structure

This study presents experimental results of compression after impact (CAI) strength testing of aluminum core sandwich structure with carbon/epoxy face sheets impacted at three different energies with either a 12.7 mm hemispherical, 24.5 mm hemispherical or sharp tip impactor. This study was undertaken to verify whether design allowables typically generated by blunt (hemispherical) impactors may be valid in ‘real world” applications where an impact may not be by a blunt object of a specific size. Results of practical interest in this study were that the visual damage was much easier to see for the sharp impactor, the damage size as detected by thermography was smaller for the sharp impactor for a given impact energy and dent depth was greater for the sharp impactor. The CAI strength results showed that the sharp impactor gave about the same CAI strength values at all three impact energy levels used. The larger hemispherical impactor gave slightly higher CAI results than the smaller blunt impactor. Overall it was deemed difficult to develop a CAI allowable that would cover all impactor shapes with any fidelity and thus using a lower bound strain allowable is suggested.

compression after impact (CAI)↗

Real-Time System Verification by Kappa-Induction

We report the first formal verification of a reintegration protocol for a safety-critical, fault-tolerant, real-time distributed embedded system. A reintegration protocol increases system survivability by allowing a node that has suffered a fault to regain state consistent with the operational nodes. The protocol is verified in the Symbolic Analysis Laboratory (SAL), where bounded model checking and decision procedures are used to verify infinite-state systems by k-induction. The protocol and its environment are modeled as synchronizing timeout automata. Because k-induction is exponential with respect to k, we optimize the formal model to reduce the size of k. Also, the reintegrator's event-triggered behavior is conservatively modeled as time-triggered behavior to further reduce the size of k and to make it invariant to the number of nodes modeled. A corollary is that a clique avoidance property is satisfied.

Pike, Lee S.↗

Randomized Adiabatic Quantum Linear Solver Algorithm with Optimal Complexity Scaling and Detailed Running Costs

Solving linear systems of equations is a fundamental problem with a wide variety of applications across many fields of science, and there is increasing effort to develop quantum linear solver algorithms. Subaşı et al. [Phys. Rev. Lett. 122, 060504 (2019)] proposed a randomized algorithm inspired by adiabatic quantum computing, based on a sequence of random Hamiltonian simulation steps, with suboptimal scaling in the condition number 𝜅 of the linear system and the target error 𝜖. Here we go beyond these results in several ways. Firstly, using filtering [Lin and Tong, Quantum 4, 361 (2020)] and Poissonization techniques [Cunningham and Roland, ArXiv:2406.03972 (2024)], the algorithm complexity is improved to the optimal scaling 𝑂⁡(𝜅⁢log (1/𝜖))—an exponential improvement in 𝜖, and a shaving of a log 𝜅 scaling factor in 𝜅. Secondly, the algorithm is further modified to achieve constant factor improvements, which are vital as we progress towards hardware implementations on fault-tolerant devices. We introduce a cheaper randomized walk operator method replacing Hamiltonian simulation—which also removes the need for potentially challenging classical precomputations; randomized routines are sampled over optimized random variables; circuit constructions are improved. We obtain a closed formula rigorously upper bounding the expected number of times one needs to apply a block-encoding of the linear system matrix to output a quantum state encoding the solution to the linear system. The upper bound is 837⁢𝜅 at 𝜖 = 10 −10 for Hermitian matrices.

97 MATHEMATICS AND COMPUTING↗

Arsenic stress triggers active exudation of arsenic–phytochelatin complexes from Lupinus albus roots

Abstract Arsenic (As) contamination of soils threatens the health of millions globally through accumulation in crops. While plants detoxify As via phytochelatin (PC) complexation and efflux of arsenite from roots, arsenite efflux mechanisms are not fully understood. Here, white lupin (Lupinus albus) was grown in semi-hydroponics, and exudation of glutathione (GSH) derivatives and PCs in response to As was measured using LC-MS/MS. Inhibiting synthesis of the PC precursor GSH with l-buthionine sulfoximine (BSO) or ABC transporters with vanadate drastically reduced (>22%) GSH derivative and PC2 exudation, but not PC3 exudation. This was accompanied by As hypersensitivity in plants treated with BSO and moderate sensitivity with vanadate treatment. Investigating As–PC complexation revealed two distinct As–PC complexes, As bound to GSH and PC2 (GS–As–PC2) and As bound to PC3 (As–PC3), in exudates of As-treated lupin plants. Vanadate inhibited As–PC exudation, while BSO inhibited both the synthesis and exudation of As–PC complexes. These results demonstrate a role for GSH derivatives and PC exudation in lupin As tolerance and reveal As–PC exudation as a new potential mechanism contributing to active As efflux in plants. Overall, this study uncovers insights into rhizosphere As detoxification with potential to help mitigate pollution and reduce As accumulation in crops.

Plant Sciences↗

University of Missouri Research Reactor (MURR) LEU Fuel Fluid-Structure Interaction Analysis

The University of Missouri Research Reactor (MURR ® ) is one of five U.S. high performance research reactors (USHPRR), plus one critical facility, that are actively collaborating with the National Nuclear Security Administration (NNSA) Material Management and Minimization (M 3 ) Reactor Conversion Program to convert from highly enriched uranium (HEU, ≥ 20 wt.% U-235) to low-enriched uranium (LEU, < 20 wt.% U-235) fuel. A new type of LEU fuel with very high density, based on an alloy of uranium and 10 weight percent molybdenum (U-10Mo), is expected to allow the conversion to LEU of USHPRR that have been found unable to be converted with previously qualified uranium silicide-aluminum (U 3 Si 2 -Al) dispersion fuel. MURR has been working with the USHPRR Reactor Conversion (RC) Pillar at Argonne National Laboratory to perform fuel element design and fuel cycle performance analyses, steady-state thermal hydraulics safety analyses, and accident safety analyses in preparation for the conversion of MURR and to support a preliminary Safety Analysis Report (SAR) for conversion to LEU fuel. In this work, Fluid-structure interaction (FSI) analysis at the fuel element level, as compared to the fuel plate level of the previous work. is performed which models all components of the MURR LEU fuel element, including fuel plates and the supporting structures e.g., side plates, end fittings, and combs. Therefore, the effect of supporting structures on the coolant flow distribution, the fuel plate deflection, and the resulting coolant channel gap reduction can be evaluated. In addition to the nominal element geometry and flow rate, the tolerances in the geometry dimensions of coolant channel and plate thickness, the effect of a comb on plate deflection, and the uncertainty of the flow rate per element are considered in this work. The effect of comb on plate displacement is quantified through two bounding cases: the case assuming a perfect bond between the comb and plates and the case neglecting the comb effect. Note that in this analysis, the FSI has been decoupled from the other structural effects caused by irradiation (e.g., swelling and irradiation creep). Assessment of combined effects is planned for a later stage of this project.

11 NUCLEAR FUEL CYCLE AND FUEL MATERIALS↗

Extending the Licklider Transmission Protocol to Multi-Band Links

Most deep space missions return data to Earth using links operating at a single frequency band. Indeed, their data requirements are low enough that bandwidth regulations do not constrain the system. In contrast, spacecraft such as Kepler or Europa Clipper are transitioning to a new operational paradigm where engineering and science data are transmitted through simultaneous links operating at different frequency bands (henceforth termed multi-band links). This ensures, for instance, that critical data is correctly received using a well characterized X-band link, while science data at a much larger data rate can be returned efficiently (both in terms of bandwidth and energy) through a Ka-band link.Having a spacecraft establish two simultaneous links with a ground station opens a large span of potential improvements for space communications and mission operations. In this paper, we consider the problem of running a Licklider Transmission Protocol (LTP) session over a multi-band link. LTP is an implementation of a selective Automatic Repeat reQuest (ARQ) protocol, i.e. it ensures correct delivery of data over an error prone link with potentially long propagation delays. To maximize its efficiency in deep space environments, LTP operates in deferred-ACK mode and is typically included as one of the core protocols in the Delay Tolerant Networking (DTN) suite.The contributions of this paper are as follows: First, we propose an extension to LTP for multi-band links (denoted MBLTP) and sketch how it can be implemented without modifying the current definition of LTP data units. Next, we develop bounds on the performance of MBLTP when transmitting a single data file over a multi-band link. Three metrics are considered, file expected delivery time, total energy spent and bundle jitter. The results of the analytic model are first benchmarked against simulations to ensure validity, and then compared against the performance of both traditional LTP and Parallel LTP (PLTP).We demonstrate that MBLTP can significantly reduce the latency and jitter with which data products are delivered to destination over a deep space link compared to LTP at moderate energy cost. Similarly, we also demonstrate that MBLTP outperforms PLTP in all considered metrics.

Sanchez Net, Marc↗

The application of emulation techniques in the analysis of highly reliable, guidance and control computer systems

Emulation techniques can be a solution to a difficulty that arises in the analysis of the reliability of guidance and control computer systems for future commercial aircraft. Described here is the difficulty, the lack of credibility of reliability estimates obtained by analytical modeling techniques. The difficulty is an unavoidable consequence of the following: (1) a reliability requirement so demanding as to make system evaluation by use testing infeasible; (2) a complex system design technique, fault tolerance; (3) system reliability dominated by errors due to flaws in the system definition; and (4) elaborate analytical modeling techniques whose precision outputs are quite sensitive to errors of approximation in their input data. Use of emulation techniques for pseudo-testing systems to evaluate bounds on the parameter values needed for the analytical techniques is then discussed. Finally several examples of the application of emulation techniques are described.

Migneault, Gerard E.↗

Derivation and experimental verification of clock synchronization theory

The objective of this work is to validate mathematically derived clock synchronization theories and their associated algorithms through experiment. Two theories are considered, the Interactive Convergence Clock Synchronization Algorithm and the Mid-Point Algorithm. Special clock circuitry was designed and built so that several operating conditions and failure modes (including malicious failures) could be tested. Both theories are shown to predict conservative upper bounds (i.e., measured values of clock skew were always less than the theory prediction). Insight gained during experimentation led to alternative derivations of the theories. These new theories accurately predict the clock system's behavior. It is found that a 100% penalty is paid to tolerate worst case failures. It is also shown that under optimal conditions (with minimum error and no failures) the clock skew can be as much as 3 clock ticks. Clock skew grows to 6 clock ticks when failures are present. Finally, it is concluded that one cannot rely solely on test procedures or theoretical analysis to predict worst case conditions. conditions.

INTERACTIVE CONVERGENCE CLOCK↗

Fast causal multicast

A new protocol is presented that efficiently implements a reliable, causally ordered multicast primitive and is easily extended into a totally ordered one. Intended for use in the ISIS toolkit, it offers a way to bypass the most costly aspects of ISIS while benefiting from virtual synchrony. The facility scales with bounded overhead. Measured speedups of more than an order of magnitude were obtained when the protocol was implemented within ISIS. One conclusion is that systems such as ISIS can achieve performance competitive with the best existing multicast facilities - a finding contradicting the widespread concern that fault-tolerance may be unacceptably costly.

Birman, Kenneth P.↗