Breaking Good: Fracture Modes for Realtime Destruction

Drawing a direct analogy with the well-studied vibration or elastic modes, we introduce an object's fracture modes, which constitute its preferred or most natural ways of breaking. We formulate a sparsified eigenvalue problem, which we solve iteratively to obtain the n lowest-energy modes. These can be precomputed for a given shape to obtain a prefracture pattern that can substitute the state of the art for realtime applications at no runtime cost but significantly greater realism. Furthermore, any realtime impact can be projected onto our modes to obtain impact-dependent fracture patterns without the need for any online crack propagation simulation. We not only introduce this theoretically novel concept, but also show its fundamental and practical superiority in a diverse set of examples and contexts

Interesting Case of Opalski Syndrome a Variant of Lateral Medullary Syndrome

ABSTRACT Lateral medullary (or Wallenberg's) syndrome is characterized by vertigo, diplopia, dysarthria, Horner`s syndrome, numbness (ipsilateral face and contralateral limb) and traditionally it is not associated with any limb weakness. Localization in this syndrome is easy because of characteristic presentation, exclusive blood supply and very small area of involvement. In our case patient had features of lateral medullary syndrome with ipsilateral hemiparesis .In Opalski syndrome hemiplegia is ipsilateral due to the extension of the infarct caudally to involve the corticospinal fibers after the pyramidal decussation. Opalski syndrome is a rare variant of Wallenberg's syndrome with ipsilateral hemiparesis. It should not be diagnosed in the absence of hyperreflexia or Babinski sign. Excessive alcohol intake may play a role in the etiopathogenesis of posterior circulation stroke

The RAGNYA fold: a novel fold with multiple topological variants found in functionally diverse nucleic acid, nucleotide and peptide-binding proteins

Using sensitive structure similarity searches, we identify a shared α+β fold, RAGNYA, principally involved in nucleic acid, nucleotide or peptide interactions in a diverse group of proteins. These include the Ribosomal proteins L3 and L1, ATP-grasp modules, the GYF domain, DNA-recombination proteins of the NinB family from caudate bacteriophages, the C-terminal DNA-interacting domain of the Y-family DNA polymerases, the uncharacterized enzyme AMMECR1, the siRNA silencing repressor of tombusviruses, tRNA Wybutosine biosynthesis enzyme Tyw3p, DNA/RNA ligases and related nucleotidyltransferases and the Enhancer of rudimentary proteins. This fold exhibits three distinct circularly permuted versions and is composed of an internal repeat of a unit with two-strands and a helix. We show that despite considerable structural diversity in the fold, its representatives show a common mode of nucleic acid or nucleotide interaction via the exposed face of the sheet. Using this information and sensitive profile-based sequence searches: (1) we predict the active site, and mode of substrate interaction of the Wybutosine biosynthesis enzyme, Tyw3p, and a potential catalytic role for AMMECR1. (2) We provide insights regarding the mode of nucleic acid interaction of the NinB proteins, and the evolution of the active site of classical ATP-grasp enzymes and DNA/RNA ligases. (3) We also present evidence for a bacterial origin of the GYF domain and propose how this version of the fold might have been utilized in peptide interactions in the context of nucleoprotein complexes

ST1710–DNA complex crystal structure reveals the DNA binding mechanism of the MarR family of regulators

ST1710, a member of the multiple antibiotic resistance regulator (MarR) family of regulatory proteins in bacteria and archaea, plays important roles in development of antibiotic resistance, a global health problem. Here, we present the crystal structure of ST1710 from Sulfolobus tokodaii strain 7 complexed with salicylate, a well-known inhibitor of MarR proteins and the ST1710 complex with its promoter DNA, refined to 1.8 and 2.10 Å resolutions, respectively. The ST1710–DNA complex shares the topology of apo-ST1710 and MarR proteins, with each subunit containing a winged helix-turn-helix (wHtH) DNA binding motif. Significantly large conformational changes occurred upon DNA binding and in each of the dimeric monomers in the asymmetric unit of the ST1710–DNA complex. Conserved wHtH loop residues interacting with the bound DNA and mutagenic analysis indicated that R89, R90 and K91 were important for DNA recognition. Significantly, the bound DNA exhibited a new binding mechanism

Dual targeting of CD19 and CD22 with Bicistronic CAR-T cells in Patients with Relapsed/Refractory Large B Cell Lymphoma

Relapse following CD19-directed chimeric antigen receptor T-cells (CAR-T) for relapsed/refractory large B-cell lymphoma (r/r LBCL) is commonly ascribed to antigen loss or CAR-T exhaustion. Multi-antigen targeting and PD-1 blockade are rational approaches to prevent relapse. Here, we test CD19/22 dual-targeting CAR-T (AUTO3) plus pembrolizumab in r/r LBCL as inpatient or outpatient therapy (NCT03289455, https://clinicaltrials.gov/ct2/show/NCT03289455). Endpoints include toxicity (primary) and response rates (secondary). AUTO3 was manufactured for 62 patients using autologous leukapheresis, modified with a bicistronic transgene. 52 patients received AUTO3 (7/52,50x106; 45/52,150-450x106) and 48/52 received pembrolizumab. Median age was 59 years (range,27-83) and 46/52 had stage III/IV disease. Median follow-up was 21.6 months (range,15.1-51.3) at last data cut (Feb 28, 2022). AUTO3 was safe: grade 1-2 and grade 3 CRS affected 18/52 (34.6%) and 1/52 (1.9%) patients, neurotoxicity arose in 4 patients (2/4, grade 3-4), HLH affected 2 patients, and no Pembrolizumab-associated autoimmune sequalae were observed. On this basis, outpatient administration was tested in 20 patients, saving a median of 14 hospital days/patient. AUTO3 was effective: overall response rates were 66% (48.9%, CR; 17%, PR). For patients with CR, median DOR was not reached, with 54.4% (CI: 32.8, 71.7) projected to remain progression-free beyond 12 months after onset of remission. DOR for all responding patients was 8.3 months (95% CI: 3.0, NE) with 42.6% projected to remain progression-free beyond 12 months after onset of remission. Overall, AUTO3 +/- pembrolizumab for r/r LBCL was safe, lending itself to outpatient administration, and delivered durable remissions in 54.4% of complete responders, associated with robust CAR-T expansion. Neither dual-targeting CAR-T nor pembrolizumab prevented relapse in a significant proportion of patients, and future developments include next-generation-AUTO3, engineered for superior expansion/persistence in vivo, and selection of CAR binders active at low antigen densities

Optimized Hot-Mix Asphalt Lift Configuration for Performance

R27-204Researchers conducted eight large-scale laboratory tests to assess the combined impact of hot-mix asphalt (HMA) overlay mix and thickness on its performance to control reflective cracking. Bonding efficiency, flexibility, and stiffness of the HMA mix as well as overlay thickness significantly affect an overlay\u2019s performance against reflective cracking. Researchers developed a generalized 3D finite-element model to predict an overlay\u2019s reflective cracking potential and generated a database of 128 cases. They also developed a data-driven surrogate model to predict reflective cracking potential that engineers can easily use. Life-cycle cost analysis of overlay alternatives was performed using Illinois Department of Transportation\u2019s unit prices from contracts between 2018 and 2019. The researchers identified optimal overlay configurations to control reflective cracking. An overlay composed of a 1.5 in (38.1 mm) SMA-9.5 or 1.25 in (31.8 mm) IL-9.5FG surface course and a 0.75 in (19.1 mm) IL-4.75 binder course had the lowest annual cost per mile among non-interstate projects. For interstate projects, an overlay composed of a 2 in (50.8 mm) SMA-12.5 surface course and a 2.25 in (57.2 mm) IL-19.0 binder course was the most cost-effective. The study concluded that to control reflective cracking and to reduce life-cycle cost, an overlay composed of an SMA-9.5 surface course and an IL-4.75 binder course is recommended for non-interstate projects. An IL-9.5FG surface course and an IL-4.75 binder course are suggested for low-volume and low-speed roads. For interstate projects, an overlay comprised of an SMA-12.5 surface course and an IL-19.0 binder course is recommended. A data-driven surrogate model may be used to design overlay thicknesses

Chromatin compaction in terminally differentiated avian blood cells: the role of linker histone H5 and non-histone protein MENT

Chromatin has a tendency to shift from a relatively decondensed (active) to condensed (inactive) state during cell differentiation due to interactions of specific architectural and/or regulatory proteins with DNA. A promotion of chromatin folding in terminally differentiated avian blood cells requires the presence of either histone H5 in erythrocytes or non-histone protein, myeloid and erythroid nuclear termination stage-specific protein (MENT), in white blood cells (lymphocytes and granulocytes). These highly abundant proteins assist in folding of nucleosome arrays and self-association of chromatin fibers into compacted chromatin structures. Here, we briefly review structural aspects and molecular mode of action by which these unrelated proteins can spread condensed chromatin to form inactivated regions in the genome

Oil Retention and Pressure Drop of R134a, R1234yf and R410A with POE 100 in Suction Lines

An experimental investigation of oil retention and pressure drop characteristics for R1234yf, R134a and R410A with POE 100 is presented, for horizontal and vertical suction lines of 10.2 mm internal diameter. Conditions of operation include a saturation temperature of 13 °C and a superheat of 15 °C, with the superficial vapor velocity and the Oil in Circulation Ratio (OCR) both varied in the range of 1-6 m/s and 1-5 % respectively. The effect of lubricant viscosity on oil retention and pressure drop is also presented by comparing results with those of POE 32, under the same conditions of operation

Investigation of oil retention and pressure drop in suction lines using R1234yf, R134a and R410A with POE ISO 100

Compressors of typical vapor compression refrigeration systems require the presence of oil, primarily for the purpose of lubrication. A small portion of this oil is transported out of the compressor by the high velocity refrigerant vapor exiting the compressor or by the refrigerant forming an equilibrium mixture with the oil. This results in a refrigerant/oil liquid mixture being circulated in the system, thereby leading to a decrease in system performance in terms of heat transfer coefficient and pressure drop. Of particular interest is studying the retention of oil at suction lines to the compressor, where conditions lead to a mixture that is rich in oil, consequently leading to high oil retention due to high mixture viscosity. The current work presents experimental data for oil retention and pressure drop in suction lines using R1234yf, the low Global Warming Potential (GWP) refrigerant which was developed as a consequence of the European Union’s Mobile Air-Conditioning Directive. Tests were conducted in 10.2 mm internal diameter horizontal and vertical suction lines that were about 2 m long, using POE ISO 100 lubricant. A saturation temperature of 13 °C and a superheat of 15 °C were employed, while the superficial refrigerant vapor velocity was varied between 1-6 m/s. Experiments were also performed in R134a in order to study if R1234yf is a suitable drop-in replacement for R134a. Also, comparisons were made with data obtained using POE ISO 32 to study the effect of lubricant viscosity. Experimental tests in R410A using POE 32 and POE 100 served as data for further comparison. Results show that at similar operating conditions, the more viscous POE 100 yields upto 40 % more oil retention and upto 60 % more pressure drop in comparison to POE 32. It was also observed that at a similar system cooling capacity, R1234yf had upto 15 % more oil retention and upto 60 % more pressure drop in comparison to R134a. A semi-empirical model has also been proposed in order to predict oil retention and pressure drop in vertical suction lines. An improved critical mass flux is also predicted in order to properly design vertical suction line sizes. Flow visualization studies were also performed in order to identify various regimes and the transitions between different regimes