gebhart/patrepeval huggingface dataset:
Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors (2015)

REPLACE is a unique strategy developed to more effectively target protein-protein interactions (PPIs). It aims to expand available drug target space by providing improved methodology for the identification of inhibitors for such binding sites and which represent the majority of potential drug targets. The main goal of this paper is to provide a methodological overview of the use and application of the REPLACE strategy which involves computational and synthetic chemistry approaches. REPLACE is exemplified through its application to the development of non-ATP competitive cyclin dependent kinases (CDK) inhibitors as anti-tumor therapeutics. CDKs are frequently deregulated in cancer and hence are considered as important targets for drug development. Inhibition of CDK2/cyclin A in S phase has been reported to promote selective apoptosis of cancer cells in a p53 independent manner through the E2F1 pathway. Targeting the protein-protein interaction at the cyclin binding groove (CBG) is an approach which will allow the specific inhibition of cell cycle over transcriptional CDKs. The CBG is recognized by a consensus sequence derived from CDK substrates and tumor suppressor proteins termed the cyclin binding motif (CBM). The CBM has previously been optimized to an octapeptide from p21Waf (HAKRRIF) and then further truncated to a pentapeptide retaining sufficient activity (RRLIF). Peptides in general are not cell permeable, are metabolically unstable and therefore the REPLACE (REplacement with Partial Ligand Alternatives through Computational Enrichment) strategy has been applied in order to generate more drug-like inhibitors. The strategy begins with the design of Fragment ligated inhibitory peptides (FLIPs) that selectively inhibit cell cycle CDK/cyclin complexes. FLIPs were generated by iteratively replacing residues of HAKRRLIF/RRLIF with fragment like small molecules (capping groups), starting from the N-terminus (Ncaps), followed by replacement on the C-terminus. These compounds are starting points for the generation of non-ATP competitive CDK inhibitors as anti-tumor therapeutics.
The cAMP-specific phosphodiesterase TbPDE2C is an essential enzyme in bloodstream form<i>Trypanosoma brucei</i> (2002)

Chemotherapy of human sleeping sickness, a fatal disease caused by the protozoan parasite Trypanosoma brucei, is in a dismal state, and the identification and characterization of new drug targets is an urgent prerequisite for an improvement of the dramatic situation in the field. Over the last several years, inhibitors of cyclic nucleotide-specific phosphodiesterases have proven to be highly successful drug candidates for an assortment of clinical conditions. Their potential as antiparasitic drugs has not been explored so far. This study reports the characterization of a cAMP-specific phosphodiesterase from T. brucei, TbPDE2C. This enzyme is a class I phosphodiesterase, and it is a member of a small enzyme family in T. brucei, TbPDE2. Inhibitors of this enzyme block the proliferation of bloodstream form trypanosomes in culture. RNA interference experiments demonstrated that the TbPDE2 family, and in particular TbPDE2C, are essential for maintaining intracellular cAMP concentrations within a physiological range. Bloodstream form trypanosomes are exquisitely sensitive to elevated concentrations of intracellular cAMP, and a disruption of TbPDE2C function quickly leads to the disruption of nuclear and cellular cell division, and to cell death. TbPDE2C might represent a novel drug target for the development of new and effective trypanocidal drugs.
Colistin: an antibiotic and its role in multiresistant Gram-negative infections. (2015)

Increasing number of infection cases caused by multiresistant Gram-negative bacteria or multidrug resistant organism (MDRO) has become a major problem worldwide since there have been a lot of resistance to many classes of antibiotics. Mutant isolates such as fluoroquinolone-resistant and -lactamase-resistant bacteria have been commonly found, particularly in intensive care unit (ICU). During the last two decades, there has been no study of developing antibiotics in search of discovering new type of antibiotics; meanwhile, the resistance of Gram-negative bacteria or MDRO to antibiotics is increasing. Colistin or polymyxin E is an old antibiotic, which has been used since 1959 for treating infection caused by Gram-negative MDRO. It was revealed that colistin has side effects of nephrotoxicity and neurotoxicity; therefore, the use of this antibiotic was stopped and it was replaced by other antibiotics which were effective and were considered safer at that time. There is an increasing number of infections with multi-resistant Gram-negative (MDRO) against the available antibiotics and the availability of alternative antibiotics has not been satisfying; therefore, microbiologists are searching back to the old option, which has been proven to be effective against multi-resistant Gram-negative bacteria, the old antibiotic that has been long forgotten, i.e. colistin, as an alternative treatment against Gram-negative MDRO. It is expected that colistin may have essential and reliable role as future antibiotics for treatment of multi-resistant Gram-negative infections and as an alternative of antibiotics that have been available so far.
Thermal Atomic Layer Etching of ZnO by a “Conversion-Etch” Mechanism Using Sequential Exposures of Hydrogen Fluoride and Trimethylaluminum (2017)

The atomic layer etching (ALE) of ZnO thin films was demonstrated using sequential, self-limiting thermal reactions with hydrogen fluoride (HF) and trimethylaluminum (TMA) as the reactants. The initial polycrystalline ZnO films were grown by atomic layer deposition (ALD) using diethylzinc (DEZ) and H2O at 150 °C. The thermal ZnO ALE process was then studied between 205 and 295 °C using various techniques. In situ quartz crystal microbalance (QCM) measurements monitored ZnO ALE at 265 °C. The ZnO etching was linear versus number of ALE cycles. The HF exposure caused a mass gain of ΔMHF = +53 ng/cm2 from fluorination. The subsequent TMA exposure caused a large mass loss of ΔMTMA = −172 ng/cm2. This mass loss was much larger than expected from metal fluoride removal resulting from ligand-exchange transmetalation. The large mass loss suggested that there is a “conversion-etch” mechanism where TMA also converts the ZnO surface to an Al2O3 surface layer. This conversion reaction is believed to occur according to 3ZnO + 2Al(CH3)3 → Al2O3 + 3Zn(CH3)2. The ALE reaction would then proceed by Al2O3 + 6HF + 4Al(CH3)3 → 6AlF(CH3)2 + 3H2O. In this etching process, the Al2O3 layer is first fluorinated by HF to produce an AlF3 surface layer. The AlF3 surface layer is then removed by ligand-exchange transmetalation with TMA to yield volatile AlF(CH3)2 reaction products. After the AlF3 removal, TMA then reacts with additional ZnO to regenerate the Al2O3 surface layer. The average mass change per cycle (MCPC) during ZnO ALE was −119 ng/cm2 at 265 °C. This MCPC corresponds to an etch rate of 2.11 Å/cycle using a ZnO film density of 5.62 g/cm3. The QCM measurements showed that the sequential HF and TMA reactions were self-limiting versus reactant exposure. Ex situ spectroscopic ellipsometry (SE) determined that the etch rates were temperature dependent, and the etch rates leveled off at higher temperatures. The etch rates ranged from 0.01 Å/cycle at 205 °C to 2.19 Å/cycle at 295 °C. Atomic force microscopy (AFM) measurements observed that the ZnO ALD films were smoothed by ZnO ALE. The conversion-etch mechanism may occur during the ALE of other metal compounds. This conversion-etch mechanism reaction may expand the number of materials that can be etched by thermal ALE methods.
<title>Rapid Texture Identification</title> (1980)

A method is presented for classifying each pixel of a textured image, and thus for segmenting the scene. The "texture energy" approach requires only a few convolutions with small (typically 5x5) integer coefficient masks, followed by a moving-window absolute average operation. Normalization by the local mean and standard deviation eliminates the need for histogram equalization. Rotation-invariance can also be achieved by using averages of the texture energy features. The convolution masks are separable, and can be implemented with 1-dimensional (vertical and horizontal) or multipass 3x3 convolutions. Special techniques permit rapid processing on general-purpose digital computers.
Homology modeling and structure-based design improve hydrophobic interaction chromatography behavior of integrin binding antibodies (2018)

Monoclonal antibody (mAb) candidates from high-throughput screening or binding affinity optimization often contain mutations leading to liabilities for further development of the antibody, such as aggregation-prone regions and lack of solubility. In this work, we optimized a candidate integrin α11-binding mAb for developability using molecular modeling, rational design, and hydrophobic interaction chromatography (HIC). A homology model of the parental mAb Fv region was built, and this revealed hydrophobic patches on the surface of the complementarity-determining region loops. A series of 97 variants of the residues primarily responsible for the hydrophobic patches were expressed and their HIC retention times (RT) were measured. As intended, many of the computationally designed variants reduced the HIC RT compared to the parental mAb, and mutating residues that contributed most to hydrophobic patches had the greatest effect on HIC RT. A retrospective analysis was then performed where 3-dimentional protein property descriptors were evaluated for their ability to predict HIC RT using the current series of mAbs. The same descriptors were used to train a simple multi-parameter protein quantitative structure-property relationship model on this data, producing an improved correlation. We also extended this analysis to recently published HIC data for 137 clinical mAb candidates as well as 31 adnectin variants, and found that the surface area of hydrophobic patches averaged over a molecular dynamics sample consistently correlated to the experimental data across a diverse set of biotherapeutics.
Overhaul of ieee 802.11 modeling and simulation in ns-2 (2007)

NS-2, with its IEEE 802.11 support, is a widely utilized simulation tool for wireless communications researchers. However, the current NS-2 distribution code has some significant shortcomings both in the overall architecture and the modeling details of the IEEE 802.11 MAC and PHY modules. This paper presents a completely revised architecture and design for these two modules. The resulting PHY is a full featured generic module able to support any single channel frame-based communications (i.e. it is also able to support non-IEEE 802.11 based MAC). The key features include cumulative SINR computation, preamble and PLCP header processing and capture, and frame body capture. The MAC accurately models the basic IEEE 802.11 CSMA/CA mechanism, as required for credible simulation studies. The newly designed MAC models transmission and reception coordination, backoff management and channel state monitoring in a structured and modular manner. In turn, the contributions of this paper make extending the MAC for protocol researches much easier and provide for a significantly higher level of simulation accuracy.
A review on software testing approaches for cloud applications (2016)

Cloud computing has actually been invented to be the latest computing standard that will work several distinctive research areas, such as software testing. Testing cloud applications will keep its unique characteristics that involve more recent testing techniques. Software testing helps to reduce the need for hardware and software services and also provide adaptable and valuable cloud platform. Testing within the cloud platform is easily manageable based on new test models and criteria. Prioritization approach is made responsive to build much better relationship between test cases. These test cases are clustered dependent on priority level. The resources can be used properly by applying load balancing algorithm. Cloud guarantees maximum usage of existing resources. But, security defined as a primary problem in cloud. At the present time, organizations are progressively moving excited about deploying and making use of ready-prepared business applications, with particular short-term to the marketplace. The possible lack of capital budgets for software planning and on principle deployments, along with the swift progression of cloud these are the reasons why one should make the interest on business application. However, these are the interests that help make the SaaS based business application on-demand. In this paper different approaches has been discussed that will help to extend the cloud environment. Also, the study of several well-known software testing approaches.
Material-Independent Mechanochemical Effect in the Deformation of Highly-Strain-Hardening Metals (2018)

``Gummy'' metals that are both soft and highly strain-hardening, like aluminum, iron, nickel, and stainless steels, are quite difficult to cut, owing to very large deformation forces and poor surface quality. The authors show how this difficulty, a consequence of unsteady plastic flow, can be overcome using a mechanochemical effect: changes in deformation promoted by a suitable coating. From glues to inks, applying any of a host of household media to the metal's surface induces a change in flow mode via a local ductile-to-brittle transition, which strongly enhances cutting. These results have wide-ranging implications for industrial machining and forming processes.
An Interactive Drilling Simulator for Teaching and Research (1995)

Abstract An interactive program has been constructed that allows a student or engineer to simulate the drilling of an oil well, and to optimize the drilling process by comparing different drilling plans. The program operates in a very user-friendly way, with emphasis on menu and button-driven commands. The simulator may be run either as a training program, with exercises that illustrate various features of the drilling process, as a game, in which a student is set a challenge to drill a well with minimum cost or time under constraints set by an instructor, or as a simulator of a real situation to investigate the merit of different drilling strategies. It has three main parts, a Lithology Editor, a Settings Editor and the simulation program itself. The Lithology Editor allows the student, instructor or engineer to build a real or imaginary sequence of rock layers, each characterized by its mineralogy, drilling and log responses. The Settings Editor allows the definition of all the operational parameters, ranging from the drilling and wear rates of particular bits in specified rocks to the costs of different procedures. The simulator itself contains an algorithm that determines rate of penetration and rate of wear of the bit as drilling continues. It also determines whether the well kicks or fractures, and assigns various other "accident" conditions. During operation, a depth vs. time curve is displayed, together with a "mud log" showing the rock layers penetrated. If desired, the well may be "logged", casings may be set and pore and fracture pressure gradients may be displayed. During drilling, the total time and cost are shown, together with cost per foot in total and for the current bit run. A demonstration version of the program is available on the World Wide Web at the Berkeley Petroleum Engineering Page. Its current address is: msel6.mse.berkeley.edu
Color plane slicing and its applications to motion characterization for machine vision (2009)

In this paper we propose the color plane slicing method, a technique to achieve a higher temporal resolution of a phenomena of interest than what is typically achievable by cameras. This is done by using a color camera and strobe lights of different colors at small intervals of time apart. The method, although simple, poses several advantages and applications to machine vision sensors which currently only inspect objects but do not characterize their motion in the context of automation and inspection. Although, the color information is traded for temporal information, we show that the framework is not restrictive for objects with or without colors. Also, the system can continue to be used as a traditional camera for quality inspection with a local translation applied to the formed composite image. Further, potential applications are discussed wherein the system is appended to an industrial grade Smart camera for ease of use. The applicability of the technique is also shown for motion characterization and vibration measurement.
A Low Dropout regulator using current buffer compensation technique (2010)

A current buffer compensation Low Dropout (LDO) regulator for portable applications is present in this paper. The current buffer compensation scheme is a current feedback amplifier, which provides low output impendence in order to move the non-dominant pole due to the large gate capacitance of the pass transistor of the LDO regulator to high frequency. This LDO circuit had been designed and implemented in a 0.35-μm CMOS processes, it occupied a chip area of 810×572 μm <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> . The measurement results show that this circuit functions properly with supply voltage of 2.2~3.3 V and provides maximum current of 200 mA. The output voltage can be adjusted from 0.6 V to 3.1 V when the supply voltage is 3.3 V.
Coding guidelines for pipelined processors (1982)

This paper is a tutorial for assembly language programmers of pipelined processors. It describes the general characteristics of pipelined processors and presents a collection of coding guidelines for them. These guidelines are particularly significant to compiler developers who determine object code patterns.
Chemically immobilized T4-bacteriophage for specific Escherichia coli detection using surface plasmon resonance (2010)

A bioassay platform using T4 bacteriophage (T4) as the specific receptor and surface plasmon resonance (SPR) as the transduction technique has been developed for the detection of Escherichia coli K12 bacteria. The T4 phages have been covalently immobilized onto gold surfaces using a self-assembled monolayer of dithiobis(succinimidyl propionate) (DTSP). Substrates of BSA/EA-T4/DTSP/Au prepared using different T4 phage concentrations have been characterized using scanning electron microscopy (SEM). The studies reveal that the use of DTSP results in a uniform binding of T4 phages onto the surface. The SPR analysis demonstrates that these BSA/EA-T4/DTSP/Au interfaces can detect the E. coli K12 with high specificity against non-host E. coli NP10 and NP30. Results of SEM and SPR studies indicate that the maximum host bacterial capture is obtained when 1.5 × 10(11) pfu ml(-1) concentration of T4 phages was used for immobilization. The surface of these chemically anchored phage substrates can be regenerated for repeated detection of E. coli K12 and can be used for detection in 7 × 10(2) to 7 × 10(8) cfu ml(-1) range. The results of these studies have implications for the development of online bioassays for the detection of various food and water borne pathogens using the inherent selectivity of bacteriophage recognition.
Conformation of Glycopeptides and Glycoproteins (2007)

Abstract ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.
Conciliating remote home network access and MAC-address control (2012)

Users are increasingly nomadic and want to access their home network from anywhere. Such remote access might also be granted for family members or friends and controlled by the home network owner on a per device basis. This paper describes an overall sound solution for a layer 2 VPN, providing one-click access to the home network. Layer 2 VPN transports all home network protocols, including multicast, UPnP, Windows shares, thus providing full home network experience to remote users. Our solution addresses several practical and technical is- sues such as MAC address filtering and IP collisions. Our solution enables in particular per-device security policy enforcement while sharing the same access credentials with several remote users. We implemented and tested the solution by extending OpenVPN and a home gateway.
Crystal Structure of the High-Pressure Phase of Solid CO <sub>2</sub> (1994)

X-ray diffraction study of solid CO(2) at room temperature has shown that the powder pattern of the high-pressure phase, which supersedes the low-pressure cubic Pa3 phase at about 10 gigapascals, is consistently interpreted in terms of an orthorhombic Cmca structure. The orthorhombic cell at 11.8 gigapascals has dimensions of 4.330 +/- 0.015, 4.657 +/- 0.005, 5.963 +/- 0.009 angstroms for its a, b, and c faces, respectively, and a volume of 120.3 +/- 0.5 cubic angstroms. Four molecules contained in the unit cell are located at the base-centered positions with their molecular axes inclined at about 52 degrees with respect to the crystallographic c axis. The volume change associated with the Pa3-Cmca transition is close to zero. The structural dimensions obtained for the high-pressure crystalline phase of CO(2) are of great importance for a theoretical understanding of the role of intermolecular interactions, including quadrupole-quadrupole interactions, in molecular condensation.
Real-time programming on accelerator many-core processors (2013)

Multi-core platforms are challenging the way software is developed, in all application domains. For the particular case of real-time systems, models for the development of parallel software must be able to be shown correct in both functional and non-functional properties at design-time. In particular, issues such as concurrency, timing behaviour and interaction with the environment need to be addressed with the same caution as for the functional requirements. This paper proposes an execution model for the parallelization of real-time software, based upon a fine-grained parallelism support being proposed to Ada, a programming language particularly suited to the development of critical, concurrent software. We also show the correctness of the proposed model in terms of satisfying constraints related to execution order and unbounded priority inversions.
Identification and Localization of Deoxyribonuclease I in the Rat Ovary1 (1997)

Our objective was to identify the endonuclease responsible for DNA degradation in the ovary and determine its localization relative to the developmental state of ovarian follicles. Immature rats were treated with diethylstilbestrol (DES; DES group), DES + eCG (eCG group) or DES + eCG + hCG (hCG group). Nuclei of the eCG and hCG but not the DES group contained a 32/34-kDA DNase I-like endonuclease activity that was Ca2+/Mg(2+)-dependent, stimulated by Mn2+, optimal at pH 7, and identified by anti-DNase I antibody. G-actin, Zn2+, dithiothreitol, aurintricarboxylic acid, and sodium aurothiomalate, but not iodoacetic acid, inhibited the activity. Addition of eCG nuclear protein extracts to nuclei from the DES group induced oligonucleosomal DNA fragmentation, which could be prevented by pretreatment of the extracts with anti-DNase I antibody. DNase I was immunolocalized in nuclei of healthy luteal cells, antral follicle granulosa cells, oocytes of preantral follicles, atretic preantral follicles, and testicular spermatogonia, but was not observed in granulosa cells of preantral follicles, theca cells, antral follicle oocytes, or testicular spermatocytes. Nuclear extracts of rat kidney, liver, and spleen, and bovine, chicken, and human ovaries displayed DNase I-like activity. These results suggest that an endonuclease indistinguishable from DNase I is responsible for ovarian apoptotic DNA degradation.