gebhart/patrepeval huggingface dataset:
Novel Cryptophycin Antitumor Agents:  Synthesis and Cytotoxicity of Fragment “B” Analogues (1999)

A general synthetic approach to novel cryptophycin analogues 6 is described. N-Hydroxysuccinimide active ester 15, a key common intermediate, was converted to beta-epoxide 6 in three steps, via initial coupling with unprotected amino acid 9, followed by deprotection/macrolactamization of acyclic precursor 16, and final oxidation of styrene 7 to install the C7-C8 beta-epoxide. Cryptophycin styrenes 7 and beta-epoxides 6, bearing diverse side chains in fragment "B", were evaluated for cytotoxic activity. beta-Epoxides 6, in general, were significantly more potent than the corresponding alpha-epoxides 17 and styrenes 7. A benzyl side chain was required for potent activity, with beta-epoxide 6u, possessing a 3-Cl,4-(dimethylamino)benzyl moiety, as the most potent cytotoxic agent prepared, with an IC(50) = 54 pM, only 2-fold less than that of Cryptophycin-52 (3).
Structure and Functional Analysis of the RNA- and Viral Phosphoprotein-Binding Domain of Respiratory Syncytial Virus M2-1 Protein (2012)

Respiratory syncytial virus (RSV) protein M2-1 functions as an essential transcriptional cofactor of the viral RNA-dependent RNA polymerase (RdRp) complex by increasing polymerase processivity. M2-1 is a modular RNA binding protein that also interacts with the viral phosphoprotein P, another component of the RdRp complex. These binding properties are related to the core region of M2-1 encompassing residues S58 to K177. Here we report the NMR structure of the RSV M2-1(58-177) core domain, which is structurally homologous to the C-terminal domain of Ebola virus VP30, a transcription co-factor sharing functional similarity with M2-1. The partial overlap of RNA and P interaction surfaces on M2-1(58-177), as determined by NMR, rationalizes the previously observed competitive behavior of RNA versus P. Using site-directed mutagenesis, we identified eight residues located on these surfaces that are critical for an efficient transcription activity of the RdRp complex. Single mutations of these residues disrupted specifically either P or RNA binding to M2-1 in vitro. M2-1 recruitment to cytoplasmic inclusion bodies, which are regarded as sites of viral RNA synthesis, was impaired by mutations affecting only binding to P, but not to RNA, suggesting that M2-1 is associated to the holonucleocapsid by interacting with P. These results reveal that RNA and P binding to M2-1 can be uncoupled and that both are critical for the transcriptional antitermination function of M2-1.
<i>VERDANDI</i> Is a Direct Target of the MADS Domain Ovule Identity Complex and Affects Embryo Sac Differentiation in <i>Arabidopsis</i>   (2010)

In Arabidopsis thaliana, the three MADS box genes SEEDSTICK (STK), SHATTERPROOF1 (SHP1), and SHP2 redundantly regulate ovule development. Protein interaction studies have shown that a multimeric complex composed of the ovule identity proteins together with the SEPALLATA MADS domain proteins is necessary to determine ovule identity. Despite the extensive knowledge that has become available about these MADS domain transcription factors, little is known regarding the genes that they regulate. Here, we show that STK, SHP1, and SHP2 redundantly regulate VERDANDI (VDD), a putative transcription factor that belongs to the plant-specific B3 superfamily. The vdd mutant shows defects during the fertilization process resulting in semisterility. Analysis of the vdd mutant female gametophytes indicates that antipodal and synergid cell identity and/or differentiation are affected. Our results provide insights into the pathways regulated by the ovule identity factors and the role of the downstream target gene VDD in female gametophyte development.
Computational analysis of filament polymerization dynamics in cytoskeletal networks (2019)

Abstract The polymerization–depolymerization dynamics of cytoskeletal proteins play essential roles in the self-organization of cytoskeletal structures, in eukaryotic as well as prokaryotic cells. While advances in fluorescence microscopy and in vitro reconstitution experiments have helped to study the dynamic properties of these complex systems, methods that allow to collect and analyze large quantitative datasets of the underlying polymer dynamics are still missing. Here, we present a novel image analysis workflow to study polymerization dynamics of active filaments in a non-biased, highly automated manner. Using treadmilling filaments of the bacterial tubulin FtsZ as an example, we demonstrate that our method is able to specifically detect, track and analyze growth and shrinkage of polymers, even in dense networks of filaments. We believe that this automated method can facilitate the analysis of a large variety of dynamic cytoskeletal systems, using standard time-lapse movies obtained from experiments in vitro as well as in the living cell. Moreover, we provide scripts implementing this method as supplementary material.
Power to the people? The true costs of choice (2007)

Frustration with public services often relates to the lack of personal attention and service: the treatment of individuals as an undifferentiated mass of people who should be grateful for what the state provides. Queuing and rationing quickly induce this kind of relationship.
BioBits™ Explorer: A modular synthetic biology education kit (2018)

Hands-on demonstrations greatly enhance the teaching of science, technology, engineering, and mathematics (STEM) concepts and foster engagement and exploration in the sciences. While numerous chemistry and physics classroom demonstrations exist, few biology demonstrations are practical and accessible due to the challenges and concerns of growing living cells in classrooms. We introduce BioBits™ Explorer, a synthetic biology educational kit based on shelf-stable, freeze-dried, cell-free (FD-CF) reactions, which are activated by simply adding water. The FD-CF reactions engage the senses of sight, smell, and touch with outputs that produce fluorescence, fragrances, and hydrogels, respectively. We introduce components that can teach tunable protein expression, enzymatic reactions, biomaterial formation, and biosensors using RNA switches, some of which represent original FD-CF outputs that expand the toolbox of cell-free synthetic biology. The BioBits™ Explorer kit enables hands-on demonstrations of cutting-edge science that are inexpensive and easy to use, circumventing many current barriers for implementing exploratory biology experiments in classrooms.
Opportunity of CMOS FD-SOI for RF power amplifier (2017)

This paper reports the design of a 5GHz WiFi power amplifier (PA) taking advantage of the FD-SOI technology. Fabricated in a 28nm UTBB FD-SOI process with 1.8-V thick oxide devices, the PA output exhibits 23dBm Psat, 18dBm under low distortion with a 3.7V power supply. The core occupies less than 1mm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> while integrating transformer and baluns.
Control of semicontinuous emulsion copolymerization reactors (1997)

Abstract The problem of simultaneous control of composition and molecular weight of copolymers produced in semicontinuous emulsion polymerization is addressed. A first‐principles model of emulsion copolymerization is used to produce optimal open‐loop policies, which are then experimentally tested on the system methyl methacrylate/vinyl acetate. In contrast to earlier work in the control of semicontinuous emulsion copolymerization, the control problem addressed has multiple inputs and multiple outputs, and the experimental application is free of empirical correlations and performed on an unseeded system. Optimal open‐loop policies are calculated efficiently by optimizing properties of the instantaneous polymer being formed. The experimental results confirm the feasibility of these techniques. A model‐predictive control scheme, in which optimal policies are recomputed on‐line to account for disturbances, is proposed. The scheme, which exploits the advantages of the efficient calculation of optimal policies, is tested by simulation showing good performance.
OFDM high speed channel complex gains estimation using Kalman filter and QR-detector (2008)

This paper deals with the case of a high speed mobile receiver operating in an orthogonal-frequency-division-multiplexing (OFDM) communication system. Assuming the knowledge of delay-related information, we propose an iterative algorithm for joint multi-path Rayleigh channel complex gains and data recovery in fast fading environments. Each complex gain time-variation, within one OFDM symbol, is approximated by a polynomial representation. Based on the Jakes process, an auto-regressive (AR) model of the polynomial coefficients dynamics is built, making it possible to employ the Kalman filter estimator for the polynomial coefficients. Hence, the channel matrix is easily computed, and the data symbol is estimated with free inter-sub-carrier-interference (ICI) thanks to the use of a QR-decomposition of the channel matrix. Our claims are supported by theoretical analysis and simulation results, which are obtained considering Jakes¿ channels with high Doppler spreads.
The effect of low sulfate concentrations on the glycosaminoglycan synthesis in anatomically intact articular cartilage of the mouse (1989)

We have studied the effect of environmental sulfate concentration on the glycosaminoglycan synthesis of anatomically intact patellar cartilage of the mouse in vitro. Incubation of mouse patellae in medium with sulfate concentrations below 0.5 mM resulted in a diminished incorporation of sulfate but in unaltered incorporation of glucosamine. This suggested the synthesis of undersulfated glycosaminoglycans under these conditions. We characterized glycosaminoglycans synthesized at three different sulfate concentrations: a sulfate concentration physiological for the mouse (1.0 mM), a sulfate concentration in the range where sulfate incorporation was strongly diminished (0.1 mM), and an extremely low sulfate concentration (10 nM). Analysis of glycosaminoglycan disaccharides and DEAE anion chromatography of the glycosaminoglycans could not confirm the synthesis of undersulfated glycosaminoglycans at 0.1 mM. The chromatogram of glycosaminoglycans synthesized in medium containing 10 nM showed the presence of a very low sulfated glycosaminoglycan pool not observed at higher medium sulfate concentrations. Intermediately sulfated glycosaminoglycans were also synthesized during incubation with 10 nM sulfate. So, our data indicate that only very low sulfate concentrations in the medium lead to the synthesis of undersulfated glycosaminoglycans and that the sulfation mechanism of murine patellar cartilage chondrocytes does not seem to fit completely in an "all-or-nothing" pattern.
Human Chemokines as Antimicrobial Peptides with Direct Parasiticidal Effect on Leishmania mexicana In Vitro (2013)

Chemokines and chemokine receptor-mediated effects are important mediators of the immunological response and cure in human leishmaniasis. However, in addition to their signalling properties for leukocytes, many chemokines have also been shown to act directly as antimicrobial peptides on bacteria and fungi. We screened ten human chemokines (CXCL2, CXCL6, CXCL8, CXCL9, CXCL10, CCL2, CCL3, CCL20, CCL27, CCL28) for antimicrobial effects on the promastigote form of the protozoan parasite Leishmania mexicana, and observed direct parasiticidal effects of several, CCL28 being the most potent. Damage to the plasma membrane integrity could be visualised by entrance of propidium iodide, as measured with flow cytometry, and by scanning electron microscopy, which showed morphological changes and aggregation of cells. The findings were in concordance with parasiticidal activity, measured by decreased mitochondrial activity in an MTT-assay. This is the first report of direct antimicrobial activity by chemokines on parasites. This component of immunity against Leishmania parasites identified here warrants further investigation that might lead to new insight in the mechanisms of human infection and/or new therapeutic approaches.
Performance and accuracy of hardware-oriented native-, emulated- and mixed-precision solvers in FEM simulations (2007)

In this survey paper, we compare native double precision solvers with emulated- and mixed-precision solvers of linear systems of equations as they typically arise in finite element discretisations. The emulation utilises two single float numbers to achieve higher precision, while the mixed precision iterative refinement computes residuals and updates the solution vector in double precision but solves the residual systems in single precision. Both techniques have been known since the 1960s, but little attention has been devoted to their performance aspects. Motivated by changing paradigms in processor technology and the emergence of highly-parallel devices with outstanding single float performance, we adapt the emulation and mixed precision techniques to coupled hardware configurations, where the parallel devices serve as scientific co-processors. The performance advantages are examined with respect to speedups over a native double precision implementation (time aspect) and reduced area requirements for a chip (space aspect). The paper begins with an overview of the theoretical background, algorithmic approaches and suitable hardware architectures. We then employ several conjugate gradient (CG) and multigrid solvers and study their behaviour for different parameter settings of the iterative refinement technique. Concrete speedup factors are evaluated on the coupled hardware configuration of a general-purpose CPU and a graphics processor. The dual performance aspect of potential area savings is assessed on a field programmable gate array (FPGA). In the last part, we test the applicability of the proposed mixed precision schemes with ill-conditioned matrices. We conclude that the mixed precision approach works very well with the parallel co-processors gaining speedup factors of four to five, and area savings of three to four, while maintaining the same accuracy as a reference solver executing everything in double precision.
Supramolecular organogel formation triggered by acid–base interaction in two-component system consisting of l-lysine derivative and aliphatic acids (2007)

The formation of supramolecular organogels using an acid–base interaction was investigated in organogelation systems consisting of Nε-lauroyl-L-lysine ethyl ester and aliphatic acids. Although the L-lysine derivative and aliphatic acids hardly had any organogelation abilities for organic solvents and oils, the mixing of both solutions led to the formation of organogels. This is induced by the formation of organic salts. The organic salt compounds of Nε-lauroyl-L-lysine ethyl ester and aliphatic acids also exhibited a good organogelation property for oils. The transmission electron microscopic analysis demonstrates these gelators formed a helical nanofiber and created a three-dimensional network in organogels. The FT-IR studies indicate that the formation of organic salt compounds through an acid–base interaction is an important step for the organogelation.
BCIRG 007: Randomized phase III trial of trastuzumab plus docetaxel with or without carboplatin first line in HER2 positive metastatic breast cancer (MBC) (2006)

LBA516 Background: Based on preclinical synergism between docetaxel (T), carboplatin (C) and trastuzumab (H), BCIRG conducted a phase III trial for women with HER2+ MBC to evaluate efficacy and safety of H in combination with T or TC. Methods: 263 patients (pts) with HER2 FISH+ MBC were randomized to TH, (H with T 100 mg/m 2 ) or TCH, (H with T 75 mg/m 2 and C AUC=6). Chemo was given q3 wks for 8 cycles with wkly H at 2 mg/kg (loading dose of 4 mg/kg), followed by H q3 wks at 6 mg/kg until progression. Pts were stratified by centre and prior (neo) adjuvant taxane chemotherapy. Primary endpoint was TTP with 80% power (0.05 significance) to detect a 50% improvement in median TTP between the 2 arms. Secondary endpoints include overall survival, response rate, duration of response (DR), clinical benefit (CB) and safety. Results: 131 pts were treated in each arm. Pt characteristics were well balanced in both groups. Importantly, only 52% of pts received C at the protocol specified dose (RDI > 0.9). Efficacy analysis was conducted at 204 events. There was no significant difference between TH and TCH in median TTP (11.1 vs 10.4 mos, p = 0.57), ORR (73% in both arms), DR (10.7 vs 9.4 mos) and CB (67% in both arms). The most common gr 3/4 toxicities were: infection (44% vs 30%), neutropenic infection (22% vs 12%), thrombocytopenia (2% vs 15%), febrile neutropenia (12% vs 13%) asthenia (5% vs 12%), anemia (5% vs 11%), and diarrhea (2% vs 9%). Two pts died (1.5%) due to sepsis in TCH. Absolute LVEF decline > 15% were seen in 5.5% vs 6.7% of pts. One pt (0.8%) had a symptomatic CHF in TH arm Conclusions: The already effective TH regimen does not benefit from the addition of C, when the T dose in TH is 100 mg/m 2 and 75 mg/m 2 in TCH, in women with HER2+ MBC. No significant financial relationships to disclose.
Structure−Function Studies of Analogues of Parathyroid Hormone (PTH)-1−34 Containing β-Amino Acid Residues in Positions 11−13<sup>,</sup> (2002)

The 1-34 N-terminal fragments of human parathyroid hormone (PTH) and PTH-related protein (PTHrP) elicit the full spectrum of bone-relevant activities characteristic of the intact hormones. The structural elements believed to be required for receptor binding and biological activity are two helical segments, one N-terminal and one C-terminal, connected by hinges or flexible points located around positions 12 and 19. To test this hypothesis, we synthesized and characterized the following analogues of PTH-(1-34), each containing single or double substitutions with beta-amino acid residues around the putative hinge located at position 12: I. [Nle(8,18),beta-Ala(11,12),Nal(23),Tyr(34)]bPTH-(1-34)NH(2); II. [Nle(8,18),beta-Ala(12,13),Nal(23),Tyr(34)]bPTH-(1-34)NH(2); III. [Nle(8,18),beta-Ala(11),Nal(23),Tyr(34)]bPTH-(1-34)NH(2); IV. [Nle(8,18),beta-hLeu(11),Nal(23),Tyr(34)]bPTH-(1-34)NH(2); V. [Nle(8,18),beta-Ala(12), Nal(23),Tyr(34)]bPTH-(1-34)NH(2); VI. [Nle(8,18),beta-Ala(13), Nal(23),Tyr(34)]bPTH-(1-34)NH(2) (beta-hLeu = beta-homo-leucine; beta-Ala = beta-alanine; Nal = L-2-naphthyl-alanine; Nle = norleucine). Analogues I and III exhibit very low binding affinity and are devoid of adenylyl cyclase activity. Analogue II, despite its very low binding capacity is an agonist. Biological activity and binding capacity are partially restored in analogue IV, and completely restored in analogues V and VI. The conformational properties of the analogues were investigated in aqueous solution containing dodecylphosphocholine (DPC) micelles as a membrane-mimetic environment using CD, 2D-NMR, and molecular dynamics calculations. All peptides fold partially into the alpha-helical conformation in the presence of DPC micelles, with a maximum helix content in the range of 30-35%. NMR analysis reveals the presence of two helical segments, one N-terminal and one C-terminal, as a common structural motif in all analogues. Incorporation of beta-Ala dyads at positions 11,12 and 12,13 in analogues I and II, respectively, enhances the conformational disorder in this portion of the sequence but also destabilizes the N-terminal helix. This could be one of the possible reasons for the lack of biological activity in these analogues. The partial recovery of binding affinity and biological activity in analogue IV, compared to the structurally similar analogue III, is clearly the consequence of the reintroduction of Leu side-chain of the native sequence. In the fully active analogues V and VI, the helix stability at the N-terminus is further increased. Taken together, these results stress the functional importance of the conformational stability of the helical activation domain in PTH-(1-34). Contrary to expectation, insertion of a single beta-amino acid residue in positions 11, 12, or 13 in analogues III-VI does not favor a disordered structure in this portion of the sequence.
Evaluating Land Subsidence Rates and Their Implications for Land Loss in the Lower Mississippi River Basin (2015)

High subsidence rates, along with eustatic sea-level change, sediment accumulation and shoreline erosion have led to widespread land loss and the deterioration of ecosystem health around the Lower Mississippi River Basin (LMRB). A proper evaluation of the spatial pattern of subsidence rates in the LMRB is the key to understanding the mechanisms of the submergence, estimating its potential impacts on land loss and the long-term sustainability of the region. Based on the subsidence rate data derived from benchmark surveys from 1922 to 1995, this paper constructed a subsidence rate surface for the region through the empirical Bayesian kriging (EBK) interpolation method. The results show that the subsidence rates in the region ranged from 1.7 to 29 mm/year, with an average rate of 9.4 mm/year. Subsidence rates increased from north to south as the outcome of both regional geophysical conditions and anthropogenic activities. Four areas of high subsidence rates were found, and they are located in Orleans, Jefferson, Terrebonne and Plaquemines parishes. A projection of future landscape loss using the interpolated subsidence rates reveals that areas below zero elevation in the LMRB will increase from 3.86% in 2004 to 19.79% in 2030 and 30.88% in 2050. This translates to a growing increase of areas that are vulnerable to land loss from 44.3 km2/year to 240.7 km2/year from 2011 to 2050. Under the same scenario, Lafourche, Plaquemines and Terrebonne parishes will experience serious loss of wetlands, whereas Orleans and Jefferson parishes will lose significant developed land, and Lafourche parish will endure severe loss of agriculture land.
The Determinants of User’s Intention to Adopt Hyper-Converged Infrastructure Technologies: An Integrated Approach (2018)

The purpose of this study is to investigate factors that affect users' intention to adopt Hyper-Converged Infrastructure (HCI) technology in Indonesia. HCI is an infrastructure that is based on software-centric architecture combines with integrated computing, storage, virtualization and other technologies packed in one box supported by one vendor. The adoption of this technology is still low both in the world and in Indonesia. This research integrates three frameworks, namely the Task-Technology Fit (TTF), the Technology Acceptance Model (TAM) and Technology, Organization and Environment (TOE). Data from 113 respondents are analyzed using SmartPLS software, a Partial Least Square Structural Equation Model (PLS-SEM) tool. This study found that perceived ease of use, competitive pressure, and vendor support affect users' intention to use Hyper-Converged Infrastructure technology.