gebhart/patrepeval huggingface dataset:
Tough Composites Inspired by Mineralized Natural Materials: Computation, 3D printing, and Testing (2013)

Abstract Composites play an important role as structural materials in a range of engineering fields due to their potential to combine the best mechanical properties of their constituents. In biology, composites are ubiquitous and exhibit fascinating and precise architectures at fine length scales; bone, hexactinellid sponges and nacreous abalone shells are prime examples. Here, typical biological composite topologies are emulated with multi‐material 3D printing at micrometer resolution. From base materials that are brittle and exhibit catastrophic failure, synthetic composites are created with superior fracture mechanical properties exhibiting deformation and fracture mechanisms reminiscent of mineralized biological composites. This complementary computational model predictions of fracture mechanisms and trends in mechanical properties are in good agreement with the experimental findings. The reported findings confirm that specific topological arrangements of soft and stiff phases as a design mechanism enhances the mechanical behavior in composites. This study demonstrates 3D printing as a means to create fracture resistant composites. Moreover, these results indicate that one can use computer models to design composite materials to exhibit tailored fracture properties and then use 3D printing to synthesize materials with such mechanical performance.
The next generation of RNA vaccines: self-amplifying RNA (2021)

The global COVID-19 pandemic has brought tremendous momentum to the field of messenger RNA (mRNA) vaccines. The advantages of this vaccine platform, such as rapid development and high efficacy, resulted in mRNA vaccines being the first approved vaccines against COVID-19. Looking forward to the development of future vaccines, how can we make RNA vaccines even better? While improvements in the stability of the formulation and cost of the vaccine are inevitable, one of the main challenges is lowering the dose of RNA in order to avoid side effects associated with high doses of RNA. One way to do this is by using self-amplifying RNA (saRNA), a type of mRNA that encodes a replicase that copies the original strand of RNA once it’s in the cell. Here, we discuss the origins of saRNA, how it works in comparison to mRNA, current challenges in the field and the future of saRNA vaccines.
The Impact of Fortification with Conjugated Linoleic Acid (CLA) on the Quality of Fluid Milk (2003)

The effects of added conjugated linoleic acid (CLA) on the sensory, chemical, and physical characteristics of 2% total fat (wt/wt) fluid milk were studied. Milks with 2% (wt/wt) total fat (2% CLA, 1% CLA 1% milkfat, 2% milkfat) were made by the addition of cream or CLA triglyceride oil into skim milk followed by HTST pasteurization and homogenization. The effects of adding vitamin E (200 ppm) and rosemary extract (0.1% wt/wt based on fat content) were investigated to prevent lipid oxidation. HTST pasteurization resulted in a significant decrease of the cis-9/trans-11 isomer and other minor CLA isomers. The cis-9/trans-11 isomer concentration remained stable through 2 wk of refrigerated storage. A significant loss of both the cis-9/trans-11 and the cis-10/trans-12 isomers occurred after 3 wk of refrigerated storage. The loss was attributed to lipase activity from excessive microbial growth. No differences were found in hexanal or other common indicators of lipid oxidation between milks with or without added CLA (P > 0.05). Descriptive sensory analysis revealed that milks with 1 or 2% CLA exhibited low intensities of a "grassy/vegetable oil" flavor, not present in control milks. The antioxidant treatments were deemed to be ineffective, under the storage conditions of this study, and did not produce significant differences from the control samples (P > 0.05). CLA-Fortified milk had significantly lower L* and b* values compared with 2% milkfat milk. No significant differences existed in viscosity. Consumer acceptability scores (n = 100) were lower (P < 0.05) for CLA-fortified milks compared to control milks, but the addition of chocolate flavor increased acceptability (P < 0.05).
Role of Cytokines and Platelet-Activating Factor in Microvascular Immune Injury (1989)

Inflammation is usually a tightly controlled process which confines tissue damage, prevents infection, and assists in cellular regeneration. However, if the inflammatory response becomes unregulated, this normally beneficial local event may escalate into a wider malignant activity, characterized by endothelial injury, excessive cell infiltration, and vascular leakage. Due to the ability of platelet-activating factor and tumor necrosis factor to elicit the release of each other, 'prime' cell responses, and influence the activity of other cytokines, we propose that these two mediators play a pivotal role in the formation of deleterious feedback cycles leading to the above endothelial damage which may underlie pathologies such as shock, sepsis, ischemia, and asthma. Platelet-activating factor antagonists such as BN 52021 inhibit the priming and other effects induced by platelet-activating factor and thus may be of therapeutic value in such conditions.
Chemical Strengthening of Glass: Lessons Learned and Yet To Be Learned (2010)

This paper reviews the progress that has been made in our understanding of the chemical strengthening of glass by ion exchange over its nearly five decades of history. Lessons learned are briefly discussed; more importantly, those which are yet to be learned are highlighted. It is recognized that, except for detailed compositional effects, the kinetics of ion interdiffusion process and the chemical strengthening technology are reasonably well understood. However, the science of stress generation and its concurrent relaxation is far from being clear despite the elegant analogy to thermal stresses invoked by Cooper. The need to understand plasticity of glass network during accommodation of a larger invading ion is emphasized. In turn, the influence of network topology on its yield strength in shear as well as hydrostatic modes is recognized. For expanded applications under extreme conditions of loading, damage evolution in chemically strengthened glass needs to be studied. Such a study is linked to our understanding of the terms “strength,”“hardness,”“toughness,” and “brittleness” of glass.
Receptor‐mediated oral delivery of a bioencapsulated green fluorescent protein expressed in transgenic chloroplasts into the mouse circulatory system (2006)

Oral delivery of biopharmaceutical proteins expressed in plant cells should reduce their cost of production, purification, processing, cold storage, transportation, and delivery. However, poor intestinal absorption of intact proteins is a major challenge. To overcome this limitation, we investigate here the concept of receptor-mediated oral delivery of chloroplast-expressed foreign proteins. Therefore, the transmucosal carrier cholera toxin B-subunit and green fluorescent protein (CTB-GFP), separated by a furin cleavage site, was expressed via the tobacco chloroplast genome. Polymerase chain reaction (PCR) and Southern blot analyses confirmed site-specific transgene integration and homoplasmy. Immunoblot analysis and ELISA confirmed expression of monomeric and pentameric forms of CTB-GFP, up to 21.3% of total soluble proteins. An in vitro furin cleavage assay confirmed integrity of the engineered furin cleavage site, and a GM1 binding assay confirmed the functionality of CTB-GFP pentamers. Following oral administration of CTB-GFP expressing leaf material to mice, GFP was observed in the mice intestinal mucosa, liver, and spleen in fluorescence and immunohistochemical studies, while CTB remained in the intestinal cell. This report of receptor-mediated oral delivery of a foreign protein into the circulatory system opens the door for low-cost production and delivery of human therapeutic proteins.
[Suppression of reaginic antibodies]. (1977)

The primary as well as an ongoing IgE response to the haptens--2,4-dinitrophenyl (DNP) and benzylpénicilloyl (BPO) determinants--were readily abrogated in an immunologically specific manner by the administration of conjugates consisting of the corresponding hapten coupled to the isologous, non-immunogenic murine gamma globulins (MgammaG), i. e., DNP8-MgammaG or BPO9-MgammaG. The epitope density of the DNPx-MgammaG and BPOx-MgammaG was shown to play a dominant role in determining whether or not these conjugates were tolerogenic. Using the adoptive transfer system in mice, it was demonstrated that this method of immunosuppression was not due to the formation of suppressor cells, but involved the elimination of hapten specific IgE-forming Bepsilon cells or the inactivation of these cells through the blockade of their antigen binding receptors. This method of suppression of anti-hapten IgE antibodies, by the use of conjugates of haptens with isologous gamma-globulins, proved also effective in rats and dogs.
Synthesis, SAR, and Pharmacological Characterization of Brain Penetrant P2X7 Receptor Antagonists (2015)

We describe the synthesis and SAR of 1,2,3-triazolopiperidines as a novel series of potent, brain penetrant P2X7 antagonists. Initial efforts yielded a series of potent human P2X7R antagonists with moderate to weak rodent potency, some CYP inhibition, poor metabolic stability, and low solubility. Further work in this series, which focused on the SAR of the N-linked heterocycle, not only increased the potency at the human P2X7R but also provided compounds with good potency at the rat P2X7R. These efforts eventually delivered a potent rat and human P2X7R antagonist with good physicochemical properties, an excellent pharmacokinetic profile, good partitioning into the CNS, and demonstrated in vivo target engagement after oral dosing.
NMDA Receptor Subunits Have Differential Roles in Mediating Excitotoxic Neuronal Death BothIn VitroandIn Vivo (2007)

Well-documented experimental evidence from both in vitro and in vivo models of stroke strongly supports the critical involvement of NMDA receptor-mediated excitotoxicity in neuronal damage after stroke. Despite this, the results of clinical trials testing NMDA receptor antagonists as neuroprotectants after stroke and brain trauma have been discouraging. Here, we report that in mature cortical cultures, activation of either synaptic or extrasynaptic NR2B-containing NMDA receptors results in excitotoxicity, increasing neuronal apoptosis. In contrast, activation of either synaptic or extrasynaptic NR2A-containing NMDA receptors promotes neuronal survival and exerts a neuroprotective action against both NMDA receptor-mediated and non-NMDA receptor-mediated neuronal damage. A similar opposing action of NR2B and NR2A in mediating cell death and cell survival was also observed in an in vivo rat model of focal ischemic stroke. Moreover, we found that blocking NR2B-mediated cell death was effective in reducing infarct volume only when the receptor antagonist was given before the onset of stroke and not 4.5 h after stroke. In great contrast, activation of NR2A-mediated cell survival signaling with administration of either glycine alone or in the presence of NR2B antagonist significantly attenuated ischemic brain damage even when delivered 4.5 h after stroke onset. Together, the present work provides a molecular basis for the dual roles of NMDA receptors in promoting neuronal survival and mediating neuronal damage and suggests that selective enhancement of NR2A-containing NMDA receptor activation with glycine may constitute a promising therapy for stroke.
Suicide recombination substrates yield covalent lambda integrase-DNA complexes and lead to identification of the active site tyrosine. (1988)

High levels of covalent integrase-DNA complexes accumulate when suicide substrates containing a medial nick within the overlap region are nicked by lambda integrase protein. The tyrosine residue at position 342 is shown to form a covalent bond with DNA at the sites of strand exchange. A mutant integrase in which this tyrosine is changed to phenylalanine is devoid of both topoisomerase and recombinase activity but still binds to both core- and arm-type DNA binding sites with an affinity comparable to wild-type integrase. Tyrosine-342 is located within a 40-amino acid region that is conserved among 15 known recombinases comprising the "integrase family." The present results show that this small region of homology participates in catalysis of strand transfer.
A 5-GHz Mesh Interconnect for a Teraflops Processor (2007)

A multicore processor in 65-Nm technology with 80 single-precision, floatingpoint cores delivers performance in excess of a Teraflops while consuming less than 100 W. A 2D on-die mesh interconnection network operating at 5 GHz provides the high-performance communication fabric to connect the cores. The network delivers a bisection bandwidth of 2.56 Terabits per second and a per hop fall-through latency of 1 nanosecond.
Secondary Structure of Proteins Through Circular Dichroism Spectroscopy (1988)

Many bacterial clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR-associated (Cas) systems employ the dual RNA–guided DNA endonuclease Cas9 to defend against invading phages and conjugative plasmids by introducing site-specific ...Read More
Treatment of experimental mesangioproliferative glomerulonephritis with non-anticoagulant heparin: therapeutic efficacy and safety. (1997)

Treatment with conventional heparin is effective in experimental mesangioproliferative glomerulonephritis. However, the long-term effects and safety of this therapy, in particular in the presence of mesangiolysis, have not been assessed. In addition, this therapy has been hampered by bleeding complications. In the present study, therefore, we investigated the long-term effects of a short course of non-anticoagulant (NA) heparin treatment in the anti-Thy 1.1 mesangioproliferative glomerulonephritis, in which early immune-mediated mesangiolysis subsequently leads to mesangial hyperproliferation. Rats received continuous ip NA-heparin or vehicle during the active mesangioproliferative phase (Days 2 to 9; early treatment) or during the early resolution phase (Days 10 to 17; late treatment). Whereas NA-heparin in the early treatment group did not affect the glomerular macrophage, lymphocyte, or platelet influx, it did lead to significantly decreased glomerular cellularity, mesangial cell proliferation, alpha-smooth muscle actin, desmin expression (ie, markers of activated mesangial cells), and matrix accumulation as well as to persistent mesangiolytic lesions including microaneurysms. Despite this latter finding, at Day 120, NA-heparin-treated rats of the early treatment group showed significantly better renal function and less proteinuria and glomerulosclerosis than vehicle-infused rats. In contrast, late therapy with NA-heparin neither accelerated resolution of the nephritis or otherwise affected the course of the disease. We conclude that transient NA-heparin therapy is effective in mesangioproliferative glomerulonephritis, both acutely and long term, when it is initiated during the active phase of the disease. Also, NA-heparin therapy is safe even in glomerular diseases accompanied by mesangiolysis.
Classifying Java class transformations for pervasive virtualized access (2009)

The indirection of object accesses is a common theme for target domains as diverse as transparent distribution, persistence, and program instrumentation. Virtualizing accesses to fields and methods (by redirecting calls through accessor and indirection methods) allows interposition of arbitrary code, extending the functionality of an application beyond that intended by the original developer. We present class modifications performed by our RuggedJ transparent distribution platform for standard Java virtual machines. RuggedJ abstracts over the location of objects by implementing a single object model for local and remote objects. However the implementation of this model is complicated by the presence of native and system code; classes loaded by Java's bootstrap class loader can be rewritten only in a limited manner, and so cannot be modified to conform to RuggedJ's complex object model. We observe that system code comprises the majority of a given Java application: an average of 76% in the applications we study. We consider the constraints imposed upon pervasive class transformation within Java, and present a framework for systematically rewriting arbitrary applications. Our system accommodates all system classes, allowing both user and system classes alike to be referenced using a single object model.
Off-chip beam steering with a one-dimensional optical phased array on silicon-on-insulator (2009)

Optical phased arrays are versatile components enabling rapid and precise beam steering. An integrated approach is followed in which a 1D optical phased array is fabricated on silicon-on-insulator. The optical phased array consists of 16 parallel grating couplers spaced 2 mum apart. Steering in one direction is done thermo-optically by means of a titanium electrode on top of the structure using the phased array principle, while steering in the other direction is accomplished by wavelength tuning. At a wavelength of 1550 nm, continuous thermo-optical steering of 2.3 degrees and wavelength steering of 14.1 degrees is reported.
Expression of normal and mutant ras proteins in human acute leukemia. (1987)

The expression of normal and mutant ras genes in human acute leukemias was assessed by the direct analysis of p21ras polypeptides, using immunoprecipitation with monoclonal antibodies. High-resolution two-dimensional gel electrophoresis permits the identification of a wide array of activated ras alleles encoding proteins with single amino acid substitutions at any of several positions. The products of three ras genes, H-ras, N-ras, and K-ras, were detected in each of 33 specimens of fresh leukemic cells. The normal K-ras and N-ras polypeptides were substantially more abundant than H-ras p21 in all samples. In over three-fourths of the cases the total amount of p21ras exceeded that seen in control hematopoietic cell lines. The level of ras expression did not correlate simply with clinical parameters, although the two samples with the most abundant p21ras were obtained from patients with relapsed T-cell acute lymphocytic leukemia (ALL). Abnormal p21ras, consistent with oncogenic activation, was found in eight patients. Six of 11 samples from acute myelocytic leukemia (AML) patients displayed a mutant N-ras p21, while only one of 20 ALL specimens had abnormal N-ras, and one had a mutant H-ras. In every case the mutant protein comprised a minority of total p21ras. In two T-cell ALL cell lines both normal and activated N-ras gene products were expressed at equal levels. By contrast, in five fresh AML samples the abnormal N-ras protein was several-fold less abundant than the normal N-ras p21. This finding implies that only a proportion of leukemic cells in an individual patient may carry the mutant ras oncogene.
Cell and tissue culture for medical research (2000)

Basic Laboratory Set-Up and Procedures Specialized Techniques Cell Characterization and Analysis Cell Line Derivation Methods Modern Clinical Applications of Cultured Cells Appendices Index
CD8+ T cells from patients with acute multiple sclerosis display selective increase of adhesiveness in brain venules: a critical role for P-selectin glycoprotein ligand-1 (2003)

Multiple sclerosis (MS) is considered an autoimmune inflammatory disease of the central nervous system. Under physiologic conditions, we compared the adhesiveness of CD4+ and CD8+ lymphocytes from nontreated patients with acute, relapsing-remitting multiple sclerosis (RRMS) and from healthy donors. We show that in patients with RRMS CD8+, but not with RRMS CD4+, T cells display increased rolling and arrest in inflamed murine brain venules. Moreover, CD8+, but not CD4+, lymphocytes from MS patients show increased rolling on P-selectin in vitro. Anti-P-selectin glycoprotein ligand-1 (PSGL-1) antibodies dramatically block the recruitment of CD8+ cells in brain vessels of patients with MS, suggesting that PSGL-1 represents a novel pharmaceutical target that may be exploited to block the selective entrance of CD8+ cells during early inflammation. Vascular cell adhesion molecule-1 (VCAM-1), but not PSGL-1, is critical for the adhesion of CD4+ cells in MS patients, highlighting a fundamental dichotomy in the mechanisms governing the recruitment of lymphocyte subsets in RRMS. Importantly, 7-color fluorescence-activated cell sorter (FACS) analysis, together with functional data, indicates that a large fraction of CD8+ cells from MS patients display the characteristics of memory-effector phenotype. In conclusion, our results show that CD8+, but not CD4+, T cells from patients with RRMS in the acute phase of the disease display increased ability to be recruited in inflamed brain venules.
Incremental RANSAC for online relocation in large dynamic environments (2006)

Vehicle relocation is the problem in which a mobile robot has to estimate the self-position with respect to an a priori map of landmarks using the perception and the motion measurements without using any knowledge of the initial self-position. Recently, random sample consensus (RANSAC), a robust multi-hypothesis estimator, has been successfully applied to offline relocation in static environments. On the other hand, online relocation in dynamic environments is still a difficult problem, for available computation time is always limited, and for measurement include many outliers. To realize real time algorithm for such an online process, we have developed an incremental version of RANSAC algorithm by extending an efficient preemption RANSAC scheme. This novel scheme named incremental RANSAC is able to find inlier hypotheses of self-positions out of large number of outlier hypotheses contaminated by outlier measurements
Ethernet controller chip interfaces with variety of 16-bit processors (1982)

The author discusses the AM 7990 chip, a local-area network controller for Ethernet (lance). Its 48-pin MOS VLSI circuit interfaces with a wide variety of microprocessors and microcomputers, including the Z8000, 8086, 68000, and LSI-11. The on-chip DMA system, contained in the parallel interface bus, allows data packets to be transferred to and from the buffer memory without processor intervention, and the internal buffer management scheme queues the packets.
Nickel-Phosphine Complex-Catalyzed Grignard Coupling. I. Cross-Coupling of Alkyl, Aryl, and Alkenyl Grignard Reagents with Aryl and Alkenyl Halides: General Scope and Limitations (1976)

Abstract It has been established that dihalodiphosphinenickel(II) complexes exhibit extremely high catalytic activity for selective cross-coupling of Grignard reagents with aryl and alkenyl halides. This catalytic reaction can be employed in synthetic practice for reasons of simple procedures, mild reaction conditions, high yields and high purity of the coupling products, and the wide applicability to reactions involving primary and secondary alkyl (regardless of the presence or absence of β-hydrogen (s)), aryl, and alkenyl Grignard reagents and nonfused, fused, and substituted aromatic halides and haloolefins. Limitations lie in sluggish reactions between alkyl Grignard reagents and dihaloethylenes. The most effective catalysts are [Ni{(C6H5)2P(CH2)3P(C6H5)2}Cl2] for alkyl and simple aryl Grignard reagents, [Ni{(CH3)2P(CH2)2P(CH3)2}Cl2] for alkenyl and allylic Grignard reagents and [Ni{P(C6H5)3}2-Cl2] for sterically hindered aryl Grignard reagents and halides. Great stabilizing effects of phosphine ligands on the catalytic species are demonstrated by no effect observed after aging the catalyst. Organic chlorides are generally the most suitable halide in view of the reasonable reactivities and limited side reactions. Ether is favored over tetrahydrofuran as solvent. About sixty experimental results are presented and several features are discussed.