gebhart/patrepeval huggingface dataset:
Electrostatic Design of Protein–Protein Association Rates (2006)

De novo design and redesign of proteins and protein complexes have made promising progress in recent years. Here, we give an overview of how to use available computer-based tools to design proteins to bind faster and tighter to their protein-complex partner by electrostatic optimization between the two proteins. Electrostatic optimization is possible because of the simple relation between the Debye-Huckel energy of interaction between a pair of proteins and their rate of association. This can be used for rapid, structure-based calculations of the electrostatic attraction between the two proteins in the complex. Using these principles, we developed two computer programs that predict the change in k(on), and as such the affinity, on introducing charged mutations. The two programs have a web interface that is available at <webref type="url">www.weizmann.ac.il/home/bcges/PARE.html</webref> and <webref type="url">http://bip.weizmann.ac.il/hypare</webref>. When mutations leading to charge optimization are introduced outside the physical binding site, the rate of dissociation is unchanged and therefore the change in k(on) parallels that of the affinity. This design method was evaluated on a number of different protein complexes resulting in binding rates and affinities of hundreds of fold faster and tighter compared to wild type. In this chapter, we demonstrate the procedure and go step by step over the methodology of using these programs for protein-association design. Finally, the way to easily implement the principle of electrostatic design for any protein complex of choice is shown.
Molecularly targeting the PI3K-Akt-mTOR pathway can sensitize cancer cells to radiotherapy and chemotherapy (2014)

Radiotherapy and chemotherapeutic agents that damage DNA are the current major non-surgical means of treating cancer. However, many patients develop resistances to chemotherapy drugs in their later lives. The PI3K and Ras signaling pathways are deregulated in most cancers, so molecularly targeting PI3K-Akt or Ras-MAPK signaling sensitizes many cancer types to radiotherapy and chemotherapy, but the underlying molecular mechanisms have yet to be determined. During the multi-step processes of tumorigenesis, cancer cells gain the capability to disrupt the cell cycle checkpoint and increase the activity of CDK4/6 by disrupting the PI3K, Ras, p53, and Rb signaling circuits. Recent advances have demonstrated that PI3K-Akt-mTOR signaling controls FANCD2 and ribonucleotide reductase (RNR). FANCD2 plays an important role in the resistance of cells to DNA damage agents and the activation of DNA damage checkpoints, while RNR is critical for the completion of DNA replication and repair in response to DNA damage and replication stress. Regulation of FANCD2 and RNR suggests that cancer cells depend on PI3K-Akt-mTOR signaling for survival in response to DNA damage, indicating that the PI3K-AktmTOR pathway promotes resistance to chemotherapy and radiotherapy by enhancing DNA damage repair.
Microscopy analysis of bone marrow–derived osteoprogenitor cells cultured on hydrogel 3‐D scaffold (2005)

Bone marrow contains progenitor cells that are able to differentiate into several mesenchymal lineages, including bone. These cells may also provide a potential therapy for bone repair. The purpose of this study was to select the osteoprogenitor cell subpopulation from bone marrow-derived mesenchymal stem cells (MSCs) and to test the ability of a hydrogel scaffold to support growth and osteogenic differentiation. MSCs isolated from rat femur bone marrow were cultured in DMEM medium supplemented with antibiotics, FCS, and L-glutamine. Osteogenic supplements (dexamethasone, sodium beta-glycerophosphate, and ascorbic acid) were added for one, two or three weeks. A selective subpopulation of osteoprogenitor cells was identified by immunohistochemistry, general morphology, scanning electron microscopy (SEM), and energy dispersive spectroscopy (EDS). Committed osteogenic cells were transferred to a 3-D hydrogel scaffold and cultured for an additional week. In standard culture, the osteoprogenitor cells formed cell clusters identified by Alizarin red S staining and by positive osteocalcin immunostaining. The number of osteoprogenitor cells, matrix synthesis, and mineralization increased gradually up to three weeks in culture. Mineral deposition in the matrix analyzed by EDS revealed the presence of calcium and phosphate ions at a Ca/P molar ratio of 1.73 in both the osteogenic cultures and the scaffold osteoprogenitor culture. Histological preparations revealed cell clusters within the hydrogel scaffold and SEM analysis revealed cell clusters attached to the scaffold surface. It is concluded that the hydrogel scaffold can support growth and differentiation of osteogenic cultures including mineralization and can potentially serve as a bone graft substitute containing committed osteoprogenitor cells.
Proximity Cluster Trees (2008)

Hierarchical spatial data structures provide a means for organizing data for efficient processing. Most spatial data structures are optimized for performing queries, such as intersection and containment testing, on large data sets. Set-up time and complexity of these structures can limit their value for small data sets, an often overlooked yet important category in geometric processing. We present a new hierarchical spatial data structure, dubbed a proximity cluster tree, which is particularly effective on small data sets. Proximity cluster trees are simple to implement, require minimal construction overhead, and are structured for fast distance-based queries. Proximity cluster trees were tested on randomly generated sets of 2D Bézier curves and on a text-rendering application requiring minimum-distance queries to 2D glyph outlines. Although proximity cluster trees were tailored for small data sets, empirical tests show that they also perform well on large data sets.
A laminate cantilever waveguide optical switch (2012)

This paper describes the use of optical laminate optics that utilizes both passive 2-D optical elements and active components. This is demonstrated in a proof-of-concept 1×2 optical switch concept that is compatible with micro electrical mechanical systems (MEMS) fabricated in laminates. The device uses a waveguide structure that is precision cut to form a cantilever structure. The cantilever, which acts as a bendable waveguide, can be positioned into two locations to align with one of two corresponding waveguides. A light beam is directed into the front end of the cantilever which couples the signal to the tip of the cantilever. The cantilever tip can be positioned to align with one of two second waveguides, thereby sending the optical signal into a specified output. The cantilever is moved using an electromagnetic actuation force, and can be magnetically latched in position so that no further power is required to hold it in place. The unique aspect of this work is that the entire device can be fabricated using laminate technology commonly found in packaging and precision PCB foundries. This allows one to utilize materials and manufacturing methods not available to silicon processing, such as the use of a flexible polymer cantilever waveguide and magnetic materials. Further, it allows integration into printed circuits. We have demonstrated proof-of-concept for this device. This paper describes the design of the structure in laminates and shows initial results.
308-nm Excimer Laser for the Treatment of Psoriasis (2000)

With 308-nm UV-B radiation generated by an excimer laser, it is possible to clear psoriasis with as little as 1 treatment with moderately long remission. In contrast to traditional phototherapy techniques, this handheld excimer laser UV-B therapy is selectively directed toward lesional skin, thus sparing the surrounding normal skin from unnecessary radiation exposure. Treatment of other inflammatory diseases and limited psoriasis seems reasonable to pursue with this modality.
Biosynthetic (recombinant) human granulocyte-macrophage colony- stimulating factor: effect on normal bone marrow and leukemia cell lines (1986)

To examine the biologic properties of the molecule encoded by the human gene for granulocyte-macrophage colony-stimulating factor (GM-CSF), we expressed the cloned complementary DNA (cDNA) in transfected monkey COS cells and purified the resultant protein. Purified biosynthetic human GM-CSF was added to cultures of normal hematopoietic progenitor cells in semisolid media, and the resulting colonies were characterized cytochemically. Non-adherent light-density bone marrow cells from healthy adult volunteers were maximally stimulated with GM-CSF (approximately 250 pmol/L, and four types of colonies were consistently identified by aspirating the individual colonies and staining with a triple stain for specific and nonspecific esterases and eosinophilic granules. Pure neutrophilic granulocyte (G), mixed granulocyte- macrophage (GM), pure macrophage (M), and pure eosinophil (EO) colonies were observed, the mean incidences on day 8 being 70%, 20%, 5%, and 5%, and on day 14, 7.5%, 16.6%, 50.9%, and 25.0%, respectively. In all types of colonies, complete maturation to segmented forms or typical macrophages was detected. GM-CSF did not enhance the growth of BFU-E from normal peripheral blood buffy coat cells in the simultaneous presence of erythropoietin alone or erythropoietin with purified erythroid-potentiating activity. GM-CSF stimulated HL-60 and KG-1 colony formation twofold and fivefold, respectively; consistent differentiation induction towards monocytic and eosinophilic lineages was observed in HL-60 but not in KG-1. These in vitro findings indicate that GM-CSF is a multilineage stimulator for progenitor cells of G, GM, M, and EO colonies.
Preparation, chemistry, and structure of the lithium salt of the octamethyldimolybdate(II) ion (1974)

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPreparation, chemistry, and structure of the lithium salt of the octamethyldimolybdate(II) ionF. A. Cotton, J. M. Troup, T. R. Webb, D. H. Williamson, and G. WilkinsonCite this: J. Am. Chem. Soc. 1974, 96, 12, 3824–3828Publication Date (Print):June 1, 1974Publication History Published online1 May 2002Published inissue 1 June 1974https://pubs.acs.org/doi/10.1021/ja00819a020https://doi.org/10.1021/ja00819a020research-articleACS PublicationsRequest reuse permissionsArticle Views224Altmetric-Citations39LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (1)»Supporting Information Supporting Information Get e-Alerts
ChemInform Abstract: Sr3GaSb3 and Sr3InP3, Two New Zintl Phases with Complex Anions. (1988)

Abstract Both the title compounds have been prepared by annealing stoichiometric mixtures of the elements at 1270 K for 1 h (heating and cooling rates are given).
Predicting mutation score using source code and test suite metrics (2012)

Mutation testing has traditionally been used to evaluate the effectiveness of test suites and provide confidence in the testing process. Mutation testing involves the creation of many versions of a program each with a single syntactic fault. A test suite is evaluated against these program versions (mutants) in order to determine the percentage of mutants a test suite is able to identify (mutation score). A major drawback of mutation testing is that even a small program may yield thousands of mutants and can potentially make the process cost prohibitive. To improve the performance and reduce the cost of mutation testing, we propose a machine learning approach to predict mutation score based on a combination of source code and test suite metrics.
Development of the Spatial Analysis Method of Vegetation Distributions in an Urban Area in Terms of Prevention of the Fire Spreading (2009)

In this study, we developed the analysis method of vegetation distributions in terms of prevention of the fire spreading through applying a fire-spreading model. With the fire-spreading model, we analyzed the spatial relationship between vegetation distributions and buildings in the two cases: one meant ordinary situation, the other meant current vegetation distribution was removed hypothetically. The difference between the numbers of buildings burnt in the two cases was defined as the vegetation role in preventing the fire spreading. As a result, it was shown that the differences might be the spatial information that could be useful for the estimation of the vegetation role in terms of prevention of the fire spreading. Through the comparison between the analysis result and the result of field survey, the proposed method seemed to be valid for evaluation of vegetation functions for prevention of the fire spreading in an urban area.
International guide to drugs for Parkinson's disease (1995)

Pharmacotherapy of Parkinson's disease (PD) has become so effective that patients with PD can enjoy a nearly normal life, including travel for several years. The degree of international travel of patients with PD and in particular the recent increased coordination between health systems in the European community call for a detailed information on the different antiparkinsonian drugs available worldwide. To provide an overview for physicians and patients on the diversity of preparations available in the different countries, we compiled the most commonly used substances along with their size of dosage and formula in an international guide to drugs for PD.
<i>cis</i> -Acting Sequences Required for NtcB-Dependent, Nitrite-Responsive Positive Regulation of the Nitrate Assimilation Operon in the Cyanobacterium <i>Synechococcus</i> sp. Strain PCC 7942 (1998)

There are three binding sites for NtcA (nirI, nirII, and nirIII), the global nitrogen regulator of cyanobacteria, in the DNA region between the two divergently transcribed operons (nirA and nirB operons) involved in nitrate assimilation in Synechococcus sp. strain PCC 7942. Using the luxAB reporter system, we showed that nirI and nirIII, which are located 23 bp upstream from the -10 promoter element of nirA and nirB, respectively, are required for induction by nitrogen depletion of the nirA and nirB operons, respectively. The induction of nirA operon transcription was a prerequisite for the nitrite-responsive positive regulation of the transcription by NtcB, a LysR-type protein. The NtcA-binding site nirII, located in the middle of the nirA-nirB intergenic region, and a potential binding site for a LysR-type protein (TGCAN5TGCA; designated L1), located between nirI and nirII, were required for the nitrite-responsive, NtcB-dependent enhancement of nirA operon transcription. Although the requirement for the L1 site was consistent with the involvement of the LysR family protein NtcB in transcriptional regulation, NtcB did not bind to the nirA regulatory region in vitro in the presence of nitrite and NtcA, suggesting the involvement of some additional factor(s) in the regulation. An L1-like inverted repeat with the consensus sequence TGCN7GCA was conserved in the nirA promoter region of cyanobacteria, being centered at position -23 with respect to the NtcA-binding site corresponding to nirI, which suggested the common occurrence of nitrite-responsive regulation of the nitrate assimilation operon among cyanobacteria.
Adult stem cells and other cancer residents. Part II (2015)

In this review, we have attempted to generalize recent data on adult stem cells as the most likely cells, according to the current dominant paradigm, in which a predisposition to malignant degeneration occurs or, in other words, where cancer is initiated.
Possible platelet thrombi formation in dog and human femoral arteries. (1982)

Atherosclerosis is a ubiquitous condition that commonly produces vessel stenosis and progresses ultimately to vascular occlusion. It is thought by many that platelets collect on sites of atherosclerosis and exacerbate its progression. We have previously shown that platelet thrombi can form within 10 minutes in the stenosed coronary arteries of a dog and can produce acute cyclical reduction in blood flow measured with an electromagnetic flowmeter (EMF). This is followed by sudden restoration of flow as the platelet thrombus breaks loose and is carried distally (Circulation 54:365-370, 1976). In five dogs, blood flow was measured simultaneously in a femoral artery stenosed 70%, exposed proximally with an EMF, and monitored distally over intact skin with a Doppler ultrasonic flowmeter (DUF). Cyclical reductions in blood flow were detected by both the EMF and the DUF, presumably due to platelet thrombi forming in the stenosed femoral artery and then breaking loose and moving distally. These flow reductions could be consistently abolished with aspirin (ASA). In ten patients with angiographically proven substantial stenoses of the femoral or popliteal arteries who were not taking ASA, the popliteal blood flow velocity was measured with a DUF. Six of the ten patients showed cyclical blood flow velocity reductions during 30 minutes of observation. These flow velocity reductions were similar to those observed in the stenosed dog femoral arteries. One hour after taking 600 mg ASA orally, five of the six patients no longer showed flow velocity reductions. Eight male control subjects who were not on ASA and had no known stenoses had no flow velocity reductions when studied with the DUF. Since many factors, such as cigarette smoking, diabetes, and elevated plasma lipids, are known to increase human platelet aggregation, we postulate that platelet thrombi may form in stenosed peripheral arteries, hasten the development of atherosclerosis, and reduce blood flow. This postulate would be compatible with the increased incidence and accelerated development of clinically significant atherosclerosis noted in such patients. Claudication may be more than just the response to "increased demand"; thrombus degeneration may lead to the elaboration of vasospastic substances. If these findings are confirmed by further investigations, the potential for successful therapeutic intervention may be quite significant.
Benzylpiperazine derivatives. I. Syntheses and biological activities of 1-(2,3,4-trimethoxybenzyl)piperazine derivatives. (1987)

A series of 1- (2, 3, 4-trimethoxybenzyl) piperazine (trimetazidine) derivatives were prepared and tested for cerebral vasodilating activity. Almost all the compounds possess stronger activity than trimetazidine and among them, the γ-amino tertiary alcohols 6e-j exhibit potent cerebral vasodilating activities which are superior to those of cinnarizine and papaverine. Moreover, these compounds show a selective vasodilating effect on vertebral arteries.
Synthesis of 5-Homologous AZT and D4T Derivatives. (1992)

The 3'-iodonucleosides 4 have been synthesized by condensation of silylated 5-alkyluracils 2 with methyl 5-O-tert-butyldiphenylsilyl-2,3-dideoxy-3-iodo-D-threo-pentofur anoside (3). 4 was treated with sodium azide and the deprotected nucleoside 5 was subsequently obtained by treatment with tetrabutylammonium fluoride. The nucleoside 4 produced the corresponding 2',3'-didehydro-2',3'-dideoxy nucleoside 6 and 3',4'-didehydro-2',3'-dideoxy nucleoside 7 in elimination reactions on treatment with sodium methoxide.
Accessible technology for interactive systems: a new approach to spoken language research (2002)

In this paper, we argue for a paradigm shift in spoken language technology, from transcription tasks to interactive systems. The current paradigm evaluates speech recognition technology in terms of word recognition accuracy on large vocabulary transcription tasks, such as telephone conversations or media broadcasts. Systems are evaluated in international competitions, with strict rules for participation and well-defined evaluation metrics. Participation in these competitions is limited to a few elite laboratories that have the resources to develop and field systems. We propose a new, more productive and more accessible paradigm for spoken language research, in which research advances are evaluated in the context of interactive systems that allow people to perform useful tasks, such as accessing information from the World Wide Web, while driving a car. These systems are made available for daily use by ordinary citizens through telephone networks or placement in easily accessible kiosks in public institutions. It has previously been argued that this new paradigm, which focuses on the goal of universal access to information for all people, better serves the needs of the research community, as well as the welfare of our citizens. We discuss the challenges and rewards of an interactive system approach to spoken language research, and discuss our initial attempts to stimulate a paradigm shift and engage a large community of researchers through free distribution of the CSLU toolkit.
Molecular Mobilities of Instant Starch Gels Determined by Oxygen‐17 and Carbon‐13 Nuclear Magnetic Resonance (1988)

ABSTRACT The molecular mobility of both the water component and the starch component of three instant starches was determined by proton decoupled oxygen‐17 ( 17 O) and proton decoupled carbon‐13 ( 13 C) Nuclear Magnetic Resonance (NMR) spectroscopy. The effect of starch concentration and various storage conditions were studied. The molecular mobility of the water associated with each of the instant starches over all concentrations studied as measured by 17 O NMR transverse relaxation rates was not much slower than that of free or bulk water. The effect of storage conditions on the molecular mobility and conformation of the starches, as monitored by proton decoupled 17 O and 13 C NMR, was in most cases small, despite the observed differences in retrogradation among the starches.