gebhart/patrepeval huggingface dataset:
Immunoadsorption as a new therapeutic principle for treatment of dilated cardiomyopathy (2002)

Dilated cardiomyopathy (DCM) is a myocardial disease characterized by progressive d epression of myocardial contractile function, and by ventricular dilatation. Abnormalities of the cellular and humoral immune system are present in a subset of patients with myocarditis and DCM. A number of various cardiac autoantibodies against cardiac cellular proteins have been identified in patients with myocarditis and DCM. Recent clinical studies showed that removal of antibodies by immunoadsorption improves cardiac function of patients with DCM indicating that activation of the humoral immune system may play a functional role in DCM.
Nonhuman primate model for regional wave travel and reflections along aortas (1987)

Arterial pulse transmission and wave reflections were studied in five mature anesthetized baboons (Papio anubis) using multisensor micromanometry. Simultaneous pressures were recorded from the left ventricle and every 10 cm along the aorta and its terminal branches, and flow velocity was measured in the aortic root. Aortic input impedance and regional foot-to-foot and apparent phase velocities were calculated. Aortography provided dimensional data for local reflection coefficients. Regional foot-to-foot wave speeds were somewhat lower than corresponding segments in humans. Proximal aortic pressure waveforms and characteristic impedance (110 +/- 29 dyn X s X cm-5) were not characteristic of middle-aged humans. Reflection coefficients at the terminal aortic bifurcation (0.06) at the level of the renal artery branches (0.09) were less than those found in humans. We conclude that the junction of the renal artery branches and the aorta in the baboon is closely matched and represents much less of a discrete reflection site than in humans. Although the baboon may be used to study pulse transmission characteristics in the baboon, this species is not a good model for the proximal systemic reflective characteristics of normal middle-aged humans.
The design, synthesis, and evaluation of molecules that enable or enhance cellular uptake: Peptoid molecular transporters (2000)

Certain proteins contain subunits that enable their active translocation across the plasma membrane into cells. In the specific case of HIV-1, this subunit is the basic domain Tat(49-57) (RKKRRQRRR). To establish the optimal structural requirements for this translocation process, and thereby to develop improved molecular transporters that could deliver agents into cells, a series of analogues of Tat(49-57) were prepared and their cellular uptake into Jurkat cells was determined by flow cytometry. All truncated and alanine-substituted analogues exhibited diminished cellular uptake, suggesting that the cationic residues of Tat(49-57) play a principal role in its uptake. Charge alone, however, is insufficient for transport as oligomers of several cationic amino acids (histidine, lysine, and ornithine) are less effective than Tat(49-57) in cellular uptake. In contrast, a 9-mer of l-arginine (R9) was 20-fold more efficient than Tat(49-57) at cellular uptake as determined by Michaelis-Menton kinetic analysis. The d-arginine oligomer (r9) exhibited an even greater uptake rate enhancement (>100-fold). Collectively, these studies suggest that the guanidinium groups of Tat(49-57) play a greater role in facilitating cellular uptake than either charge or backbone structure. Based on this analysis, we designed and synthesized a class of polyguanidine peptoid derivatives. Remarkably, the subset of peptoid analogues containing a six-methylene spacer between the guanidine head group and backbone (N-hxg), exhibited significantly enhanced cellular uptake compared to Tat(49-57) and even to r9. Overall, a transporter has been developed that is superior to Tat(49-57), protease resistant, and more readily and economically prepared.
Frequency, pulse length, and the mechanical index (2005)

A comparison of hemolytic and sonochemical activity of ultrasonic cavitation in a rotating tube.
Replication Terminator Protein-Based Replication Fork-Arrest Systems in Various Bacillus Species (1998)

The replication terminator protein (RTP) of Bacillus subtilis interacts with its cognate DNA terminators to cause replication fork arrest, thereby ensuring that the forks approaching one another at the conclusion of a round of replication meet within a restricted terminus region. A similar situation exists in Escherichia coli, but it appears that the fork-arrest systems in these two organisms have evolved independently of one another. In the present work, RTP homologs in four species closely related to B. subtilis (B. atrophaeus, B. amyloliquefaciens, B. mojavensis, and B. vallismortis) have been identified and characterized. An RTP homolog could not be identified in another closely related species, B. licheniformis. The nucleotide and amino acid changes from B. subtilis among the four homologs are consistent with the recently established phylogenetic tree for these species. The GC contents of the rtp genes raise the possibility that these organisms arose within this branch of the tree by horizontal transfer into a common ancestor after their divergence from B. licheniformis. Only 5 amino acid residue positions were changed among the four homologs, despite an up to 17.2% change in the nucleotide sequence, a finding that highlights the importance of the precise folded structure to the functioning of RTP. The absence of any significant change in the proposed DNA-binding region of RTP emphasizes the importance of its high affinity for the DNA terminator in its functioning. By coincidence, the single change (E30K) found in the B. mojavensis RTP corresponds exactly to that purposefully introduced by others into B. subtilis RTP to implicate a crucial role for E30 in the fork-arrest mechanism. The natural occurrence of this variant is difficult to reconcile with such an implication, and it was shown directly that RTP.E30K functions normally in fork arrest in B. subtilis in vivo. Additional DNA terminators were identified in the new RTP homolog-containing strains, allowing the definition of a Bacillus terminator consensus and identification of two more terminators in the B. subtilis 168 genome sequence to bring the total to nine.
Substrate selection rules for the hairpin ribozyme determined by in vitro selection, mutation, and analysis of mismatched substrates. (1993)

Substrate recognition by the hairpin ribozyme has been proposed to involve two short intermolecular helices, termed helix 1 and helix 2. We have used a combination of three methods (cleavage of mismatched substrates, in vitro selection, and site-specific mutational analysis) to systematically determine the substrate recognition rules for this RNA enzyme. Assays measuring substrate cleavage in trans under multiple turnover conditions were conducted using the wild-type ribozyme and substrates containing mismatches in all sites potentially recognized by the ribozyme. Molecules containing single- and multiple-base mismatches in helix 2 at sites distant from the cleavage site (g-4c, u-5a, g-4c: u-5a) were cleaved with reduced efficiency, whereas those with mismatches proximal to the cleavage site (c-2a, a-3c, c-2a: a-3c) were not cut. Analogous results were obtained for helix 1, where mismatches distal from the cleavage site (u+7a, u+8a, u+9a, u+7a: u+8a: u+9a) were used much more efficiently than those proximal to the cleavage site (c+4a, u-5a, g+6c, c+4a: u+5a: g+6c). In vitro selection experiments were carried out to identify active variants from populations of molecules in which either helix 1 or helix 2 was randomized. Results constitute an artificial phylogenetic data base that proves base-pairing of nucleotides at five positions within helix 1 and three positions within helix 2 and reveals a significant sequence bias at 3 bp (c+4.G6, c-2.G11, and a-3.U12). This sequence bias was confirmed at two sites by measuring relative cleavage rates of all 16 possible dinucleotide combinations at base pairs c+4.G6 and c-2.G11.(ABSTRACT TRUNCATED AT 250 WORDS)
Thermodynamics using coins (2000)

Students often have difficulty understanding the concepts of entropy and irreversibility, and to a lesser extent, temperature. This is partially due to the statistical nature of these concepts and the abstract connection between probability and energy. The example of a large collection of coins is used to elucidate the basic concepts of probability (in particular, the law of large numbers), and uses them in the same setting to disentangle the more difficult notions of temperature, entropy, and irreversibility.
Selection of ribozymes that catalyse multiple-turnover Diels–Alder cycloadditions by using in vitro compartmentalization (2005)

In vitro compartmentalization (IVC) has previously been used to evolve protein enzymes. Here, we demonstrate how IVC can be applied to select RNA enzymes (ribozymes) for a property that has previously been unselectable: true intermolecular catalysis. Libraries containing 10(11) ribozyme genes are compartmentalized in the aqueous droplets of a water-in-oil emulsion, such that most droplets contain no more than one gene, and transcribed in situ. By coencapsulating the gene, RNA, and the substrates/products of the catalyzed reaction, ribozymes can be selected for all enzymatic properties: substrate recognition, product formation, rate acceleration, and turnover. Here we exploit the complementarity of IVC with systematic evolution of ligands by exponential enrichment (SELEX), which allows selection of larger libraries (>/=10(15)) and for very small rate accelerations (k(cat)/k(uncat)) but only selects for intramolecular single-turnover reactions. We selected approximately 10(14) random RNAs for Diels-Alderase activity with five rounds of SELEX, then six to nine rounds with IVC. All selected ribozymes catalyzed the Diels-Alder reaction in a truly bimolecular fashion and with multiple turnover. Nearly all ribozymes selected by using eleven rounds of SELEX alone contain a common catalytic motif. Selecting with SELEX then IVC gave ribozymes with significant sequence variations in this catalytic motif and ribozymes with completely novel motifs. Interestingly, the catalytic properties of all of the selected ribozymes were quite similar. The ribozymes are strongly product inhibited, consistent with the Diels-Alder transition state closely resembling the product. More efficient Diels-Alderases may need to catalyze a second reaction that transforms the product and prevents product inhibition.
Induction Magnetometers Principle, Modeling and Ways of Improvement (2012)

International audience
Macroscopic Behavior of Kraft Lignin Fractions: Melt Stability Considerations for Lignin–Polyethylene Blends (2016)

Questions that pertain to the behavior of softwood kraft lignin fractions as opposed to the whole lignin still prevail. In an effort to further understand such effects at a macroscopic level, we have examined the issue of melt stability of polyethylene (PE) in blends with fractionated and unfractionated softwood kraft lignin. While methylation of the phenolic OH groups significantly stabilizes any lignin/PE melt, more in depth data demonstrate that when separate, acetone soluble (ASKL) and acetone insoluble (AIKL) kraft lignin fractions behave completely differently than the original unfractionated material. The low molecular weight methylated ASKL offers unexpected plasticizing action to PE melts, possibly as a consequence of its low molecular weight and spherical configuration. The higher molecular weight AIKL offers relatively stable PE melts, possibly manifesting its rigid nature and higher glass transition temperature likely occurring due to π stacking operating among its aromatic rings. Mixing these two fractions together creates unstable PE melts with a propensity to extensively thermally cross-link in the absence of methylation. These findings offer for the first time insight into the nonproductive cooperative action of individual fractions in softwood kraft lignin with significant technological ramifications.
Palantir: raising awareness among configuration management workspaces (2003)

Current configuration management systems promote workspaces that isolate developers from each other. This isolation is both good and bad. It is good, because developers make their changes without any interference from changes made concurrently by other developers. It is bad, because not knowing which artifacts are changing in parallel regularly leads to problems when changes are promoted from workspaces into a central configuration management repository. Overcoming the bad isolation, while retaining the good isolation, is a matter of raising awareness among developers, an issue traditionally ignored by the discipline of configuration management. To fill this void, we have developed Palantir, a novel workspace awareness tool that complements existing configuration management systems by providing developers with insight into other workspaces. In particular, the tool informs a developer of which other developers change which other artifacts, calculates a simple measure of severity of those changes, and graphically displays the information in a configurable and generally non-obtrusive manner. To illustrate the use of Palantir, we demonstrate how it integrates with two representative configuration management systems.
Control of Lipid Accumulation in the Yeast Yarrowia lipolytica (2008)

A genomic comparison of Yarrowia lipolytica and Saccharomyces cerevisiae indicates that the metabolism of Y. lipolytica is oriented toward the glycerol pathway. To redirect carbon flux toward lipid synthesis, the GUT2 gene, which codes for the glycerol-3-phosphate dehydrogenase isomer, was deleted in Y. lipolytica in this study. This Delta gut2 mutant strain demonstrated a threefold increase in lipid accumulation compared to the wild-type strain. However, mobilization of lipid reserves occurred after the exit from the exponential phase due to beta-oxidation. Y. lipolytica contains six acyl-coenzyme A oxidases (Aox), encoded by the POX1 to POX6 genes, that catalyze the limiting step of peroxisomal beta-oxidation. Additional deletion of the POX1 to POX6 genes in the Delta gut2 strain led to a fourfold increase in lipid content. The lipid composition of all of the strains tested demonstrated high proportions of FFA. The size and number of the lipid bodies in these strains were shown to be dependent on the lipid composition and accumulation ratio.
Novel method to fabricate corrugation for a λ/4-shifted distributed feedback laser using a grating photomask (1989)

A novel method was developed to fabricate corrugation for a λ/4-shifted distributed feedback (DFB) laser. Mechanically ruled grating patterns were transferred photolithographically to the surface of an InP substrate. The resultant λ/4-shifted DFB laser operated in a single longitudinal mode at the Bragg wavelength.
Induction of alpha-smooth muscle actin by transforming growth factor-beta 1 in quiescent human breast gland fibroblasts. Implications for myofibroblast generation in breast neoplasia. (1993)

These results provide a strategy for the molecular characterization of epithelial-stromal interaction in breast neoplasia.
Text mining: a new frontier for lossless compression (1999)

Data mining, a burgeoning new technology, is about looking for patterns in data. Likewise, text mining is about looking for patterns in text. Text mining is possible because you do not have to understand text in order to extract useful information from it. Here are four examples. First, if only names could be identified, links could be inserted automatically to other places that mention the same name, links that are "dynamically evaluated" by calling upon a search engine to bind them at click time. Second, actions can be associated with different types of data, using either explicit programming or programming-by-demonstration techniques. A day/time specification appearing anywhere within one's E-mail could be associated with diary actions such as updating a personal organizer or creating an automatic reminder, and each mention of a day/time in the text could raise a popup menu of calendar-based actions. Third, text could be mined for data in tabular format, allowing databases to be created from formatted tables such as stock-market information on Web pages. Fourth, an agent could monitor incoming newswire stories for company names and collect documents that mention them, an automated press clipping service. This paper aims to promote text compression as a key technology for text mining.
Perpendicular magnetization of Co2FeAl full-Heusler alloy films induced by MgO interface (2011)

The perpendicular magnetization of Co2FeAl (CFA) full-Heusler alloy films was achieved in the structures of CFA/MgO and MgO/CFA with the perpendicular magnetic anisotropy energy density (KU) of 2–3×106 erg/cm3, which can be used as the perpendicular ferromagnetic electrodes of MgO-based magnetic tunnel junctions (MTJs) with high thermal stability at sub-50-nm dimension. The CFA thickness dependence of KU was investigated at different annealing temperatures, indicating that the perpendicular anisotropy of CFA is contributed by the interfacial anisotropy between CFA and MgO. This letter will open up a way for obtaining perpendicular magnetization of Co-based full-Heusler alloys, which is promising for further reduction in the critical current of current induced magnetization switching in MgO-based MTJ nanopillars with perpendicular full-Heusler alloy electrodes.
Layered space-time architecture for wireless communication in a fading environment when using multi-element antennas (2002)

This paper addresses digital communication in a Rayleigh fading environment when the channel characteristic is unknown at the transmitter but is known (tracked) at the receiver. Inventing a codec architecture that can realize a significant portion of the great capacity promised by information theory is essential to a standout long-term position in highly competitive arenas like fixed and indoor wireless. Use (n <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">T</inf> , n <inf xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">R</inf> ) to express the number of antenna elements at the transmitter and receiver. An (n, n) analysis shows that despite the n received waves interfering randomly, capacity grows linearly with n and is enormous. With n = 8 at 1% outage and 21-dB average SNR at each receiving element, 42 b/s/Hz is achieved. The capacity is more than 40 times that of a (1, 1) system at the same total radiated transmitter power and bandwidth. Moreover, in some applications, n could be much larger than 8. In striving for significant fractions of such huge capacities, the question arises: Can one construct an (n, n) system whose capacity scales linearly with n, using as building blocks n separately coded one-dimensional (1-D) subsystems of equal capacity? With the aim of leveraging the already highly developed 1-D codec technology, this paper reports just such an invention. In this new architecture, signals are layered in space and time as suggested by a tight capacity bound.
A phase I study of ALX148, a CD47 blocker, in combination with established anticancer antibodies in patients with advanced malignancy. (2019)

2514 Background: CD47 is a myeloid checkpoint upregulated by tumor cells to evade the host’s immune response. ALX148 (A) is a fusion protein comprised of a high affinity CD47 blocker linked to an inactive human immunoglobulin Fc region. ALX148 is well tolerated in combination with pembrolizumab (P) or trastuzumab (T) with no maximum tolerated dose (MTD) identified (ASCO 2018 #3068, SITC 2018 #P335). Safety and antitumor activity of ALX148 (10 mg/kg QW) in combination with T or P are reported in patients (pts) including those with anti-HER2 or checkpoint inhibitor (CPI) relapsed/refractory diseases. Methods: Patients with malignancy including non-small cell lung cancer (NSCLC: CPI resistant/refractory or PD-L1 tumor proportion score &lt;50%) and head and neck squamous cell carcinoma (HNSCC: progressed on platinum therapy) received A+P. Patients with HER2 malignancy including gastric/gastroesophageal junction (GEJ) cancer (progressed on T + fluoropyrimidine-based therapy) received A+T. Safety, response, pharmacokinetic (PK), and pharmacodynamic (PD) markers were assessed. Preliminary data from fully enrolled cohorts are reported as of 20 Jan 2019 (safety)/28 Jan 2019 (efficacy). Results: Seventy-nine pts received A+P (All, n=50; NSCLC, n=23; HNSCC, n=20) or A+T (All, n=29; Gastric/GEJ, n=23) as of data cutoff. Forty-seven pts reported mostly low grade treatment related adverse events. The most common were fatigue (11%), AST increase (9%), ALT increase (8%), anemia (8%), and platelets decreased (6%). In select tumor histologies, anticancer activity was observed in initial response-evaluable pts [NSCLC (n=23) 1PR, 8SD; HNSCC (n=17) 3PR, 4SD; and Gastric/GEJ (n=21) 4PR, 6SD]. Preliminary results indicate favorable ALX148 PK and CD47 target occupancy profiles, and positive effects on tumor infiltrating immune cells. Results will be updated at presentation. Conclusions: ALX148 demonstrates excellent tolerability with favorable PK/PD characteristics to date. Objective responses were observed in patients with late line NSCLC, HNSCC, and Gastric/GEJ, including disease relapsed/refractory to prior CPI and HER2-targeted therapies. Clinical trial information: NCT03013218.
Recombinant Outer Surface Protein A from Borrelia burgdorferi Induces Antibodies Protective against Spirochetal Infection in Mice (1991)

The outer surface protein A (OspA) of Borrelia burgdorferi was isolated in its native form from strains ZS7 and B31 and as a recombinant protein from strain ZS7. Amino acid sequence analysis of internal peptides of native OspA (strain ZS7) revealed identity with the sequence deduced from the OspA gene. Repeated immunization of C57BL/6 and C.B-17 mice with any of the three OspA structures resulted in the generation of monospecific hyperimmune sera reactive with both native and recombinant OspA. Upon transfer of immune sera specific for either native OspA (strain B31) or recombinant OspA (strain ZS7) but not of those reactive with the recombinant 41-kDa flagellin-associated antigen, severe combined immunodeficient (SCID) mice were completely protected against infection with strain ZS7. The finding that monoclonal antibodies to OspA and to OspB but not to non-outer surface spirochetal structures such as flagellin, p20, p65, and p70 conferred protection in SCID mice makes OspA (and possibly OspB) a promising candidate vaccine against Lyme disease.