text:
Project acronym ATMEN
Project Atomic precision materials engineering
Researcher (PI) Toma SUSI
Summary Despite more than fifty years of scientific progress since Richard Feynman's 1959 vision for nanotechnology, there is only one way to manipulate individual atoms in materials: scanning tunneling microscopy. Since the late 1980s, its atomically sharp tip has been used to move atoms over clean metal surfaces held at cryogenic temperatures. Scanning transmission electron microscopy, on the other hand, has been able to resolve atoms only more recently by focusing the electron beam with sub-atomic precision. This is especially useful in the two-dimensional form of hexagonally bonded carbon called graphene, which has superb electronic and mechanical properties. Several ways to further engineer those have been proposed, including by doping the structure with substitutional heteroatoms such as boron, nitrogen, phosphorus and silicon. My recent discovery that the scattering of the energetic imaging electrons can cause a silicon impurity to move through the graphene lattice has revealed a potential for atomically precise manipulation using the Ångström-sized electron probe. To develop this into a practical technique, improvements in the description of beam-induced displacements, advances in heteroatom implantation, and a concerted effort towards the automation of manipulations are required. My project tackles these in a multidisciplinary effort combining innovative computational techniques with pioneering experiments in an instrument where a low-energy ion implantation chamber is directly connected to an advanced electron microscope. To demonstrate the power of the method, I will prototype an atomic memory with an unprecedented memory density, and create heteroatom quantum corrals optimized for their plasmonic properties. The capability for atom-scale engineering of covalent materials opens a new vista for nanotechnology, pushing back the boundaries of the possible and allowing a plethora of materials science questions to be studied at the ultimate level of control.
Despite more than fifty years of scientific progress since Richard Feynman's 1959 vision for nanotechnology, there is only one way to manipulate individual atoms in materials: scanning tunneling microscopy. Since the late 1980s, its atomically sharp tip has been used to move atoms over clean metal surfaces held at cryogenic temperatures. Scanning transmission electron microscopy, on the other hand, has been able to resolve atoms only more recently by focusing the electron beam with sub-atomic precision. This is especially useful in the two-dimensional form of hexagonally bonded carbon called graphene, which has superb electronic and mechanical properties. Several ways to further engineer those have been proposed, including by doping the structure with substitutional heteroatoms such as boron, nitrogen, phosphorus and silicon. My recent discovery that the scattering of the energetic imaging electrons can cause a silicon impurity to move through the graphene lattice has revealed a potential for atomically precise manipulation using the Ångström-sized electron probe. To develop this into a practical technique, improvements in the description of beam-induced displacements, advances in heteroatom implantation, and a concerted effort towards the automation of manipulations are required. My project tackles these in a multidisciplinary effort combining innovative computational techniques with pioneering experiments in an instrument where a low-energy ion implantation chamber is directly connected to an advanced electron microscope. To demonstrate the power of the method, I will prototype an atomic memory with an unprecedented memory density, and create heteroatom quantum corrals optimized for their plasmonic properties. The capability for atom-scale engineering of covalent materials opens a new vista for nanotechnology, pushing back the boundaries of the possible and allowing a plethora of materials science questions to be studied at the ultimate level of control.
Project acronym CHROMABOLISM
Project Chromatin-localized central metabolism regulating gene expression and cell identity
Researcher (PI) Stefan KUBICEK
Host Institution (HI) CEMM - FORSCHUNGSZENTRUM FUER MOLEKULARE MEDIZIN GMBH
Call Details Consolidator Grant (CoG), LS3, ERC-2017-COG
Summary Epigenetics research has revealed that in the cell's nucleus all kinds of biomolecules–DNA, RNAs, proteins, protein posttranslational modifications–are highly compartmentalized to occupy distinct chromatin territories and genomic loci, thereby contributing to gene regulation and cell identity. In contrast, small molecules and cellular metabolites are generally considered to passively enter the nucleus from the cytoplasm and to lack distinct subnuclear localization. The CHROMABOLISM proposal challenges this assumption based on preliminary data generated in my laboratory. I hypothesize that chromatin-bound enzymes of central metabolism and subnuclear metabolite gradients contribute to gene regulation and cellular identity. To address this hypothesis, we will first systematically profile chromatin-bound metabolic enzymes, chart nuclear metabolomes across representative leukemia cell lines, and develop tools to measure local metabolite concentrations at distinct genomic loci. In a second step, we will then develop and apply technology to perturb these nuclear metabolite patterns by forcing the export of metabolic enzymes for the nucleus, aberrantly recruiting these enzymes to selected genomic loci, and perturbing metabolite patterns by addition and depletion of metabolites. In all these conditions we will measure the impact of nuclear metabolism on chromatin structure and gene expression. Based on the data obtained, we will model for the effects of cellular metabolites on cancer cell identity and proliferation. In line with the recent discovery of oncometabolites and the clinical use of antimetabolites, we expect to predict chromatin-bound metabolic enzymes that can be exploited as druggable targets in oncology. In a final aim we will validate these targets in leukemia and develop chemical probes against them. Successful completion of this project has the potential to transform our understanding of nuclear metabolism in control of gene expression and cellular identity.
Epigenetics research has revealed that in the cell's nucleus all kinds of biomolecules–DNA, RNAs, proteins, protein posttranslational modifications–are highly compartmentalized to occupy distinct chromatin territories and genomic loci, thereby contributing to gene regulation and cell identity. In contrast, small molecules and cellular metabolites are generally considered to passively enter the nucleus from the cytoplasm and to lack distinct subnuclear localization. The CHROMABOLISM proposal challenges this assumption based on preliminary data generated in my laboratory. I hypothesize that chromatin-bound enzymes of central metabolism and subnuclear metabolite gradients contribute to gene regulation and cellular identity. To address this hypothesis, we will first systematically profile chromatin-bound metabolic enzymes, chart nuclear metabolomes across representative leukemia cell lines, and develop tools to measure local metabolite concentrations at distinct genomic loci. In a second step, we will then develop and apply technology to perturb these nuclear metabolite patterns by forcing the export of metabolic enzymes for the nucleus, aberrantly recruiting these enzymes to selected genomic loci, and perturbing metabolite patterns by addition and depletion of metabolites. In all these conditions we will measure the impact of nuclear metabolism on chromatin structure and gene expression. Based on the data obtained, we will model for the effects of cellular metabolites on cancer cell identity and proliferation. In line with the recent discovery of oncometabolites and the clinical use of antimetabolites, we expect to predict chromatin-bound metabolic enzymes that can be exploited as druggable targets in oncology. In a final aim we will validate these targets in leukemia and develop chemical probes against them. Successful completion of this project has the potential to transform our understanding of nuclear metabolism in control of gene expression and cellular identity.
Project acronym CoMoQuant
Project Correlated Molecular Quantum Gases in Optical Lattices
Researcher (PI) Hanns-Christoph NAEGERL
Summary In a quantum engineering approach we aim to create strongly correlated molecular quantum gases for polar molecules confined in an optical lattice to two-dimensional geometry with full quantum control of all de-grees of freedom with single molecule control and detection. The goal is to synthesize a high-fidelity molec-ular quantum simulator with thousands of particles and to carry out experiments on phases and dynamics of strongly-correlated quantum matter in view of strong long-range dipolar interactions. Our choice of mole-cule is the KCs dimer, which can either be a boson or a fermion, allowing us to prepare and probe bosonic as well as fermionic dipolar quantum matter in two dimensions. Techniques such as quantum-gas microscopy, perfectly suited for two-dimensional systems, will be applied to the molecular samples for local control and local readout. The low-entropy molecular samples are created out of quantum degenerate atomic samples by well-established coherent atom paring and coherent optical ground-state transfer techniques. Crucial to this pro-posal is the full control over the molecular sample. To achieve near-unity lattice filling fraction for the mo-lecular samples, we create two-dimensional samples of K-Cs atom pairs as precursors to molecule formation by merging parallel planar systems of K and Cs, which are either in a band-insulating state (for the fermions) or in Mott-insulating state (for the bosons), along the out-of-plane direction. The polar molecular samples are used to perform quantum simulations on ground-state properties and dy-namical properties of quantum many-body spin systems. We aim to create novel forms of superfluidity, to investigate into novel quantum many-body phases in the lattice that arise from the long-range molecular dipole-dipole interaction, and to probe quantum magnetism and its dynamics such as spin transport with single-spin control and readout. In addition, disorder can be engineered to mimic real physical situations.
In a quantum engineering approach we aim to create strongly correlated molecular quantum gases for polar molecules confined in an optical lattice to two-dimensional geometry with full quantum control of all de-grees of freedom with single molecule control and detection. The goal is to synthesize a high-fidelity molec-ular quantum simulator with thousands of particles and to carry out experiments on phases and dynamics of strongly-correlated quantum matter in view of strong long-range dipolar interactions. Our choice of mole-cule is the KCs dimer, which can either be a boson or a fermion, allowing us to prepare and probe bosonic as well as fermionic dipolar quantum matter in two dimensions. Techniques such as quantum-gas microscopy, perfectly suited for two-dimensional systems, will be applied to the molecular samples for local control and local readout. The low-entropy molecular samples are created out of quantum degenerate atomic samples by well-established coherent atom paring and coherent optical ground-state transfer techniques. Crucial to this pro-posal is the full control over the molecular sample. To achieve near-unity lattice filling fraction for the mo-lecular samples, we create two-dimensional samples of K-Cs atom pairs as precursors to molecule formation by merging parallel planar systems of K and Cs, which are either in a band-insulating state (for the fermions) or in Mott-insulating state (for the bosons), along the out-of-plane direction. The polar molecular samples are used to perform quantum simulations on ground-state properties and dy-namical properties of quantum many-body spin systems. We aim to create novel forms of superfluidity, to investigate into novel quantum many-body phases in the lattice that arise from the long-range molecular dipole-dipole interaction, and to probe quantum magnetism and its dynamics such as spin transport with single-spin control and readout. In addition, disorder can be engineered to mimic real physical situations.
Project acronym MicroMOUPE
Project Microscopy - Making optimal use of photons and electrons
Researcher (PI) Thomas JUFFMANN
Summary The sensitivity of modern microscopy is limited by shot-noise. It limits the accuracy of measurements of specimen properties as well as the spatial resolution of electron microscopes when imaging sensitive specimens, such as proteins or DNA. But the shot-noise limit is not a fundamental limit. A technologically feasible and optimal approach to overcoming the shot-noise limit is to have each probe particle interact with the specimen multiple times. We recently introduced this concept to microscopy using self-imaging cavities. Within this project, I want to demonstrate post-selection free sub-shot noise microscopy with both photons and electrons. Optically this will be possible by introducing a fast electro-optical switch into a multi-pass microscope, evading the need for temporal post-selection. After this proof-of principle experiment, the sensitivity enhancement offered by multi-pass microscopy shall be applied to the detection of nanometric particles, such as single molecules, proteins and metal nanoparticles. Linear signal enhancement with the number of interactions is expected for bright-field microscopy. For dark-field microscopy a quadratic enhancement is expected, due to coherent build-up of scattered fields. Finally, adaptive optics will be used to optimize multi-pass microscopy for the study of cells. Multi-pass electron microscopy will be realized in collaboration with Stanford University. It will require several novel electron optical elements that will be designed and tested both at Stanford University and at the University of Vienna. One of these elements will be a pattern generator for electrons based on ponderomotive potentials. The required potential landscapes will be created using adaptive optics to shape intense laser pulses. With this novel electron optics tool fast beam-blanking, a phase plate for Zernike phase microscopy, arbitrary pattern creation and aberration correction will be demonstrated.
The sensitivity of modern microscopy is limited by shot-noise. It limits the accuracy of measurements of specimen properties as well as the spatial resolution of electron microscopes when imaging sensitive specimens, such as proteins or DNA. But the shot-noise limit is not a fundamental limit. A technologically feasible and optimal approach to overcoming the shot-noise limit is to have each probe particle interact with the specimen multiple times. We recently introduced this concept to microscopy using self-imaging cavities. Within this project, I want to demonstrate post-selection free sub-shot noise microscopy with both photons and electrons. Optically this will be possible by introducing a fast electro-optical switch into a multi-pass microscope, evading the need for temporal post-selection. After this proof-of principle experiment, the sensitivity enhancement offered by multi-pass microscopy shall be applied to the detection of nanometric particles, such as single molecules, proteins and metal nanoparticles. Linear signal enhancement with the number of interactions is expected for bright-field microscopy. For dark-field microscopy a quadratic enhancement is expected, due to coherent build-up of scattered fields. Finally, adaptive optics will be used to optimize multi-pass microscopy for the study of cells. Multi-pass electron microscopy will be realized in collaboration with Stanford University. It will require several novel electron optical elements that will be designed and tested both at Stanford University and at the University of Vienna. One of these elements will be a pattern generator for electrons based on ponderomotive potentials. The required potential landscapes will be created using adaptive optics to shape intense laser pulses. With this novel electron optics tool fast beam-blanking, a phase plate for Zernike phase microscopy, arbitrary pattern creation and aberration correction will be demonstrated.
Project acronym NOISE
Project Noise-Sensitivity Everywhere
Researcher (PI) Gabor Zoltan PETE
Host Institution (HI) MAGYAR TUDOMANYOS AKADEMIA RENYI ALFRED MATEMATIKAI KUTATOINTEZET
Summary Noise-sensitivity of a Boolean function with iid random input bits means that resampling a tiny proportion of the input makes the output unpredictable. This notion arises naturally in computer science, but perhaps the most striking example comes from statistical physics, in large part due to the PI: the macroscopic geometry of planar percolation is very sensitive to noise. This can be recast in terms of Fourier analysis on the hypercube: a function is noise sensitive iff most of its Fourier weight is on "high energy" eigenfunctions of the random walk operator. We propose to use noise sensitivity ideas in three main directions: (A) Address some outstanding questions in the classical case of iid inputs: universality in critical planar percolation; the Friedgut-Kalai conjecture on Fourier Entropy vs Influence; noise in First Passage Percolation. (B) In statistical physics, a key example is the critical planar FK-Ising model, with noise being Glauber dynamics. One task is to prove noise sensitivity of the macroscopic structure. A key obstacle is that hypercontractivity of the critical dynamics is not known. (C) Babai's conjecture says that random walk on any finite simple group, with any generating set, mixes in time poly-logarithmic in the volume. Two key open cases are the alternating groups and the linear groups SL(n,F2). We will approach these questions by first proving fast mixing for certain macroscopic structures. For permutation groups, this is the cycle structure, and it is related to a conjecture of Tóth on the interchange process, motivated by a phase transition question in quantum mechanics. We will apply ideas of statistical physics to group theory in other novel ways: using near-critical FK-percolation models to prove a conjecture of Gaboriau connecting the first ell2-Betti number of a group to its cost, and using random walk in random environment to prove the amenability of the interval exchange transformation group, refuting a conjecture of Katok.
Noise-sensitivity of a Boolean function with iid random input bits means that resampling a tiny proportion of the input makes the output unpredictable. This notion arises naturally in computer science, but perhaps the most striking example comes from statistical physics, in large part due to the PI: the macroscopic geometry of planar percolation is very sensitive to noise. This can be recast in terms of Fourier analysis on the hypercube: a function is noise sensitive iff most of its Fourier weight is on "high energy" eigenfunctions of the random walk operator. We propose to use noise sensitivity ideas in three main directions: (A) Address some outstanding questions in the classical case of iid inputs: universality in critical planar percolation; the Friedgut-Kalai conjecture on Fourier Entropy vs Influence; noise in First Passage Percolation. (B) In statistical physics, a key example is the critical planar FK-Ising model, with noise being Glauber dynamics. One task is to prove noise sensitivity of the macroscopic structure. A key obstacle is that hypercontractivity of the critical dynamics is not known. (C) Babai's conjecture says that random walk on any finite simple group, with any generating set, mixes in time poly-logarithmic in the volume. Two key open cases are the alternating groups and the linear groups SL(n,F2). We will approach these questions by first proving fast mixing for certain macroscopic structures. For permutation groups, this is the cycle structure, and it is related to a conjecture of Tóth on the interchange process, motivated by a phase transition question in quantum mechanics. We will apply ideas of statistical physics to group theory in other novel ways: using near-critical FK-percolation models to prove a conjecture of Gaboriau connecting the first ell2-Betti number of a group to its cost, and using random walk in random environment to prove the amenability of the interval exchange transformation group, refuting a conjecture of Katok.
Project acronym POPCRYSTAL
Project Precisely Oriented Porous Crystalline Films and Patterns
Researcher (PI) Paolo FALCARO
Host Institution (HI) TECHNISCHE UNIVERSITAET GRAZ
Summary Metal-Organic Frameworks (MOFs) are nanoporous crystalline solids with narrow pore distributions and high accessible surface areas. MOFs are typically prepared in a polycrystalline form via the self-assembly of inorganic (nodes) and organic (links) building units. This bottom-up approach allows for properties such as, pore size, topology and chemical functionality to be precisely tailored. Such synthetic control has identified MOFs as promising platform material for device fabrication in the areas of microelectronics, photonics, sensing. However, current methods for fabricating MOF films and patterns cannot generate precisely oriented crystals on commercially relevant scales (i.e. cm). Thus, limiting access to applications that require anisotropic functional properties (e.g. optics, electronics, separation). POPCRYSTAL will enable the fabrication of films and patterns composed of precisely oriented MOF crystals by exploiting crystalline ceramics to guide the aligned growth of MOF crystals. Remarkably, the scale of these heteroepitaxially grown MOFs is solely determined by the ceramic precursor which can be easily synthesized on areas covering mm2 to cm2. POPCRYSTAL will advance a proof of concept study by addressing the following important research aims: the basic understanding of the formation mechanism and rules governing the heteroepitaxial relationship (WP1), the extension to different ceramic-MOF systems (WP2), the control over crystalline porous film and pattern features (WP3) and the fabrication of a proof-of-concept that will highlight the importance of aligned pores for separation (WP4). In summary, by exploiting the heteroepitaxial growth mechanism between ceramics and MOFs POPOCRYSTAL will fabricate unprecedented crystalline MOF films and patterns with precisely oriented nanopores and nanochannels. Thus POPCRYSTAL intercrosses and connects nanoscale chemistry, controlled self-assembly on a macroscale and nanoporous-based device fabrication.
Metal-Organic Frameworks (MOFs) are nanoporous crystalline solids with narrow pore distributions and high accessible surface areas. MOFs are typically prepared in a polycrystalline form via the self-assembly of inorganic (nodes) and organic (links) building units. This bottom-up approach allows for properties such as, pore size, topology and chemical functionality to be precisely tailored. Such synthetic control has identified MOFs as promising platform material for device fabrication in the areas of microelectronics, photonics, sensing. However, current methods for fabricating MOF films and patterns cannot generate precisely oriented crystals on commercially relevant scales (i.e. cm). Thus, limiting access to applications that require anisotropic functional properties (e.g. optics, electronics, separation). POPCRYSTAL will enable the fabrication of films and patterns composed of precisely oriented MOF crystals by exploiting crystalline ceramics to guide the aligned growth of MOF crystals. Remarkably, the scale of these heteroepitaxially grown MOFs is solely determined by the ceramic precursor which can be easily synthesized on areas covering mm2 to cm2. POPCRYSTAL will advance a proof of concept study by addressing the following important research aims: the basic understanding of the formation mechanism and rules governing the heteroepitaxial relationship (WP1), the extension to different ceramic-MOF systems (WP2), the control over crystalline porous film and pattern features (WP3) and the fabrication of a proof-of-concept that will highlight the importance of aligned pores for separation (WP4). In summary, by exploiting the heteroepitaxial growth mechanism between ceramics and MOFs POPOCRYSTAL will fabricate unprecedented crystalline MOF films and patterns with precisely oriented nanopores and nanochannels. Thus POPCRYSTAL intercrosses and connects nanoscale chemistry, controlled self-assembly on a macroscale and nanoporous-based device fabrication.
Project acronym SARF
Project Single-Atom Radio Frequency Fingerprinting
Researcher (PI) Stefan MUELLEGGER
Host Institution (HI) UNIVERSITAT LINZ
Summary "Precise investigation tools for analyzing and manipulating matter down to the scale of single atoms are the eyes, ears and fingers of nanoscience and -engineering. SARF takes these nano-analytical ""senses"" one next step beyond the present state of the art. SARF is breaking new grounds by enabling spectral fingerprinting of single atoms for elemental identification and intra-molecular chemical analytics with sub-nanometer spatial resolution and operating in vacuum- as well as liquid-phase environments. This presently impossible combination of analytical capabilities simultaneously in a single tool is highly desirable to many diverse fields of nanoscience and technology, where decisive functionality originates from single individual atoms and molecules (e.g. spintronics, sensors, catalysis, medicinal drug development, surface physics, biology, etc.). SARF realizes resonance spectroscopy at giga-Hertz frequencies combined with scanning tunneling microscopy for specific single-atom fingerprinting. Characteristic resonance signals are locally detectable by the probe tip as small changes of conductance that indeed enable elemental and chemical identification. SARF conceives and develops single-atom fingerprinting on a manifold of different systems including magnetic and nonmagnetic metals, semiconductors and, exemplarily, tetrapyrrole-based metal-organic functional molecules. If successful, SARF will provide a controlled, versatile, fast and readily applicable ""atom-by-atom"" matter analysis, where single atoms are selected and identified one by one in real time and space."
"Precise investigation tools for analyzing and manipulating matter down to the scale of single atoms are the eyes, ears and fingers of nanoscience and -engineering. SARF takes these nano-analytical ""senses"" one next step beyond the present state of the art. SARF is breaking new grounds by enabling spectral fingerprinting of single atoms for elemental identification and intra-molecular chemical analytics with sub-nanometer spatial resolution and operating in vacuum- as well as liquid-phase environments. This presently impossible combination of analytical capabilities simultaneously in a single tool is highly desirable to many diverse fields of nanoscience and technology, where decisive functionality originates from single individual atoms and molecules (e.g. spintronics, sensors, catalysis, medicinal drug development, surface physics, biology, etc.). SARF realizes resonance spectroscopy at giga-Hertz frequencies combined with scanning tunneling microscopy for specific single-atom fingerprinting. Characteristic resonance signals are locally detectable by the probe tip as small changes of conductance that indeed enable elemental and chemical identification. SARF conceives and develops single-atom fingerprinting on a manifold of different systems including magnetic and nonmagnetic metals, semiconductors and, exemplarily, tetrapyrrole-based metal-organic functional molecules. If successful, SARF will provide a controlled, versatile, fast and readily applicable ""atom-by-atom"" matter analysis, where single atoms are selected and identified one by one in real time and space."
Project acronym TUCAS
Project Tuneable Catalyst Surfaces for Heterogeneous Catalysis – Electrochemical Switching of Selectivity and Activity
Researcher (PI) Christoph MAG. RER. NAT. RAMESHAN
Summary In heterogeneous catalysis surfaces decorated with uniformly dispersed, catalytically highly active particles are a key requirement for excellent performance. One of the main tasks in catalysis research is the continuous improvement or development of catalytically active materials. An emerging concept in catalyst design, and the aim of this project, is to selectively and reversibly tune and modify the surface chemistry by electrochemical polarisation. Perovskite-type catalysts raise the opportunity to incorporate guest elements as dopants. Upon electrochemical polarisation these dopants emerge from the oxide lattice to form catalytically active clusters or nanoparticles on the surface (by exsolution). In consequence this leads to a strong modification or enhancement of catalytic selectivity and activity. Electrochemical polarisation offers the possibility to adjust the surface chemistry in response to an external signal (here the applied voltage). Studies in a realistic catalytic reaction environment (in-situ) will enable a direct correlation of surface structure with catalytic activity, selectivity and the electrochemical stimulation. The unique combination of surface science, heterogeneous catalysis and electrochemistry will take this research to a new ground-breaking level. No research group has yet tried to tackle this topic on a fundamental mechanistic level by this multidisciplinary approach. The proposed project opens unprecedented possibilities for catalyst design and in-situ control due to the versatility of perovskite-type catalyst materials and dopant elements. Nanoparticle exsolution is a highly time- and cost-efficient way of catalyst preparation and it will offer solutions to major problems in heterogeneous catalysis, such as ageing (sintering) or catalyst deactivation (coking). Tuneable catalyst surfaces will facilitate tackling a major concern of the 21st century, the utilisation of CO2 and its conversion to renewable fuel.
In heterogeneous catalysis surfaces decorated with uniformly dispersed, catalytically highly active particles are a key requirement for excellent performance. One of the main tasks in catalysis research is the continuous improvement or development of catalytically active materials. An emerging concept in catalyst design, and the aim of this project, is to selectively and reversibly tune and modify the surface chemistry by electrochemical polarisation. Perovskite-type catalysts raise the opportunity to incorporate guest elements as dopants. Upon electrochemical polarisation these dopants emerge from the oxide lattice to form catalytically active clusters or nanoparticles on the surface (by exsolution). In consequence this leads to a strong modification or enhancement of catalytic selectivity and activity. Electrochemical polarisation offers the possibility to adjust the surface chemistry in response to an external signal (here the applied voltage). Studies in a realistic catalytic reaction environment (in-situ) will enable a direct correlation of surface structure with catalytic activity, selectivity and the electrochemical stimulation. The unique combination of surface science, heterogeneous catalysis and electrochemistry will take this research to a new ground-breaking level. No research group has yet tried to tackle this topic on a fundamental mechanistic level by this multidisciplinary approach. The proposed project opens unprecedented possibilities for catalyst design and in-situ control due to the versatility of perovskite-type catalyst materials and dopant elements. Nanoparticle exsolution is a highly time- and cost-efficient way of catalyst preparation and it will offer solutions to major problems in heterogeneous catalysis, such as ageing (sintering) or catalyst deactivation (coking). Tuneable catalyst surfaces will facilitate tackling a major concern of the 21st century, the utilisation of CO2 and its conversion to renewable fuel.


When I created my winter capsule wardrobe, I knew this sweater had to be included. Aside from its obviously being a sweater, it screams winter with the color work across the yoke. I've said this before and I'll say it again, one day I will learn how to knit a sweater like this. I love color work in sweaters! I like to keep the outfit simple when I wear this, since the sweater pretty much speaks for itself. I'm using my birthday present to myself — my black Michael Kors Chandler purse. I love how soft the leather is, and I can also use it as a crossbody!
What's your favorite sweater to wear during the colder months?


text:
Q: selector returning different value despite custom equalityFn check returning true I have the following selector and effect
const filterValues = useSelector<State, string[]>(
    state => state.filters.filter(f => f.field === variableId).map(f => f.value),
    (left, right) => {
        return left.length === right.length && left.every(l => right.includes(l));
    },
);
const [value, setValue] = useState<SelectionRange>({ start: null, end: null });
useEffect(() => {
    const values = filterValues
            .filter(av => av).sort((v1, v2) => v1.localeCompare(v2));
        const newValue = {
            start: values[0] ?? null,
            end: values[1] ?? null,
        };
        setValue(newValue);
}, [filterValues]);

the selector above initially returns an empty array, but a different one every time and I don't understand why because the equality function should guarantee it doesn't.
That makes the effect trigger, sets the state, the selector runs again (normal) but returns another different empty array! causing the code to run in an endless cycle.
Why is the selector returning a different array each time? what am I missing?
I am using react-redux 7.2.2

A: react-redux e-runs the selector if the selector is a new reference, because it assumes the code could have changed what it's selecting entirely
https://github.com/reduxjs/react-redux/issues/1654
one solution is to memoize the selector function
const selector = useMemo(() => (state: State) => state.filters.filter(f => f.field === variableId).map(f => f.value), [variableId]);
const filterValues = useSelector<State, string[]>(
    selector ,
    (left, right) => {
        return left.length === right.length && left.every(l => right.includes(l));
    },
);

A: You can try memoizing the result of your filter in a selector and calculate value in a selector as well, now I'm not sure if you still need the local state of value as it's just a copy of a derived value from redux state and only causes an extra render when you copy it but here is the code:

const { Provider, useDispatch, useSelector } = ReactRedux;
const { createStore, applyMiddleware, compose } = Redux;
const { createSelector, defaultMemoize } = Reselect;
const { useState, useEffect, useMemo } = React;

const initialState = {
  filters: [
    { field: 1, value: 1 },
    { field: 2, value: 2 },
    { field: 1, value: 3 },
    { field: 2, value: 4 },
  ],
};
//action types
const TOGGLE = 'NEW_STATE';
const NONE = 'NONE';
//action creators
const toggle = () => ({
  type: TOGGLE,
});
const none = () => ({ type: NONE });
const reducer = (state, { type }) => {
  if (type === TOGGLE) {
    return {
      filters: state.filters.map((f) =>
        f.field === 1
          ? { ...f, field: 2 }
          : { ...f, field: 1 }
      ),
    };
  }
  if (type === NONE) {
    //create filters again should re run selector
    //  but not re render
    return {
      filters: [...state.filters],
    };
  }
  return state;
};
//selectors
const selectFilters = (state) => state.filters;
const createSelectByVariableId = (variableId) => {
  const memoArray = defaultMemoize((...args) => args);
  return createSelector([selectFilters], (filters) =>
    memoArray.apply(
      null,
      filters
        .filter((f) => f.field === variableId)
        .map((f) => f.value)
    )
  );
};
const createSelectSelectValue = (variableId) =>
  createSelector(
    [createSelectByVariableId(variableId)],
    //?? does not work in SO because babel is too old
    (values) => ({
      start: values[0] || null,
      end: values[1] || null,
    })
  );
//creating store with redux dev tools
const composeEnhancers =
  window.__REDUX_DEVTOOLS_EXTENSION_COMPOSE__ || compose;
const store = createStore(
  reducer,
  initialState,
  composeEnhancers(
    applyMiddleware(() => (next) => (action) =>
      next(action)
    )
  )
);
var last;
const App = ({ variableId }) => {
  const selectValue = useMemo(
    () => createSelectSelectValue(variableId),
    [variableId]
  );
  const reduxValue = useSelector(selectValue);
  if (last !== reduxValue) {
    console.log('not same', last, reduxValue);
    last = reduxValue;
  }
  //not sure if you still need this, you are just
  //  copying a value you already have
  const [value, setValue] = useState(reduxValue);
  const dispatch = useDispatch();
  useEffect(() => setValue(reduxValue), [reduxValue]);
  console.log('rendering...', value);
  return (

      <button onClick={() => dispatch(toggle())}>
        toggle
      </button>
      <button onClick={() => dispatch(none())}>none</button>

{JSON.stringify(value, undefined, 2)}

  );
};

ReactDOM.render(
  <Provider store={store}>
    <App variableId={1} />
  </Provider>,
  document.getElementById('root')
);

redpajama_set_name: RedPajamaStackExchange


PRANAV SANGHAVI says, Good afternoon everyone and welcome to the chat.
PRANAV SANGHAVI answers, at 2007-04-04 12:04:20The banking stocks are under a bit of pressure due to the rising interest rates and hike in CRR also. So in the short term they will face some resistance but if you take a 1 to 2 year view I think you should be fine. RPL also will give you meaningful returns beyond 2009.
PRANAV SANGHAVI answers, Indiabulls is an aggressive player in the brokerage business. I would look at it if it corrects further. Instead of HCL I would rather look at a Wipro or TCS.
PRANAV SANGHAVI answers, If you are a longer term player you could hold on. They have some expansion plans in the pipeline.
m asked, should i buy some sbi share?
PRANAV SANGHAVI answers, Despite all the negativity the banking sector is facing, I would look at SBI but for a 2 to 3 year perspective. It is the largest public sector bank in India and there are talks of a stake sale.
vp asked, how is the performance of reliance equity fund (Hedging)?
PRANAV SANGHAVI answers, I have not studied the Fund so will not be able to help you.
PRANAV SANGHAVI answers, I cannot gie you specific names but look at funds offered by HDFC, DSPML, Templeton, SBI Mutual and especially the large cap diversified ones.
PRANAV SANGHAVI answers, I would look at INFY, IDFC and probably a HDFC Bank or SBI form current levels.
neeraj asked, Hearing a lot that market will break the level 12K...What do u think ?
PRANAV SANGHAVI answers, Markets are always very news sesitive and even in a bleak short term scenario our markets are up today on good news form the US economy. So nothing can be ruled out. If all things turn negative we could see our index at a 12 PE.
gh asked, In the recent crash, I lost Rs 50,000. Tell me the best way to recover it.
PRANAV SANGHAVI answers, I would do a litlle bit of research in the index stocks. See which ones are performing well and which will give good results for the March end and a rising interest rate scenario won't upset their earnings substantially and pick them and sit on them for 6 to 12 months.
PRANAV SANGHAVI answers, Pantaloon has two problems to look at immediately. One, the rising interest rate may reduce credit offtake which may result in lower sales for them in the times to come. Second is a lot of large foreign players are looking to enter our markets. When they do start operations in a couple of years thats when Pantaloon will be really tested.
PRANAV SANGHAVI answers, even the Rupee is strengthening I would still look at the Tech sector. And also quality stocks within the Infrastructure sector.
PRANAV SANGHAVI answers, I would pick quality fundamentally strong stocks like BHEL, L&T, INFY, TCS, Wipro, ITC and hold on to them for about 6 months. Set a price target divide your loss amount by that figure and pick up that many shares.
chander asked, I have 25 shares of Infosys @ Av price of Rs.1900. Should I hold please?
PRANAV SANGHAVI answers, Yes please do. I think they will give good results for March end.
Manish asked, Ihave bought POLARIS @ 181.10, Pls adv what to do ?
PRANAV SANGHAVI answers, I owuld either switch to a frontline tech stock or convert to cash and wait and watch.
vdatar11 asked, Sir,Femcare Pharma! Very strong set of numbers for first 9 months (31.12.06.) 1.Turnover & Net Profit being Rs.51.41 Cr.& Rs.10.18 Cr. against Rs.41.88 Cr. & Rs.6.13 Cr. 2.EPS( Not Annualised ) for the same period Rs.33.81 as against Rs.20.36 . 3.Co. exhibits Topline Growth of 22.76% & Bottomline Gr.of 66.08 % 4.Promoters holding is 68% & RONW 38% 5.Stock split & Right issue a possibility 6.Beneficiary of Domestic Cons .Boom 7.PE of 11 & Good Buyout candidate for Godrej Or HLL. Your take on such Value Pick?
PRANAV SANGHAVI answers, It seems you have done your home work well. If you do research and invest with conviction you will surely see returns on a quality stock.
raju asked, I got 1000 shares of TCS at average price of 550. What should I do.
PRANAV SANGHAVI answers, I would hold on at least till the results. If you are a short term trader which I don't think you are seeing your acquisition price, you could exit whenm market rallies 500 to 700 points. But if you are a long term investor I would stay put.
marc asked, What are the future prospects of Tech Mahindra ( long term perspective ) in light of meltdown of IT stocks in recent days and rupee appreciation.
PRANAV SANGHAVI answers, Yes Tech mahindra also may be hit by the Rupee stregnthening but in the longer term its increase in revenue and profits will outstrip the percentage rise in the Rupee. So I would look at TM with a long term outlook.
PRANAV SANGHAVI answers, They are midcap stocks which will get hit the most in times of corrections and take time to rise in times of bull runs. But Moser Baer and Mphasis look promising with a 1 year outlook.
shailesh asked, what do you say about stocks of KEI... two months back was at Rs 120 and now at Rs 67. Is it worth investing more in this stock looking at long term?
PRANAV SANGHAVI answers, I dont follow that stock, so I wouldn't be able to help you.
PRANAV SANGHAVI answers, I dont follow that stock in detail but from what the company has projected it should atleast give a20 to 30% return in a years time. But I would rather look at other textile and garmetn stocks.
aka asked, sir, what about construction stocks. They are coming down continuously. However they have visibility of earning. Specifically your view on era contruction. CMP Rs 320/- Fy07 EPS rs 75/- consolidate projected by H S Bharana the promoter. equity diluted is 23 cr. order book of 2000 cr. it is quoting at single digit PE. However Kotak, motilal etc have given buy reco but still not moving. Your comments Please.
PRANAV SANGHAVI answers, They had run up substantially in the recent run up. Also I think in some stocks the land banks were unreasonably valued. So a correction was expected. I would look at the performance over the next few quarters. Especially the residential developers.
pradeep18 asked, Hi Mr. Pranav Can you tell me that which is the best time to buy some shareof good companies.
PRANAV SANGHAVI answers, Hi Pradeep, you can buy when the markets correct on every dip. But I would wait for a while as the markets look to be extremely volatile in the short term. But you can buy in parts every time the markets are down substantially like the 600 points fall like the day before.
PRANAV SANGHAVI answers, I think the March end results will dictate where the markets move. And I personally dont see substantially lower profit figures. Although some of the banks have paid lower advance tax.
to the price as that of AirTel?
PRANAV SANGHAVI answers, I would look at Idea with a 2 year outlook atleast. See Bharti it took off after atleast 2 to 3 years of listing.
rajs asked, do u recomend picking up infy stocks?
PRANAV SANGHAVI answers, Yes at times of corrections like day before you could.
sandy asked, what us the future of Parsvnath developers, Unitech nd SRF??
PRANAV SANGHAVI answers, I like Unitech of the three but I would not look at them right now.
PRANAV SANGHAVI answers, I would look to be in cash so when a buying opportunity arises you could invest.
PRANAV SANGHAVI answers, I have mentioned quite a few stocks in my earlier replies please look up. Thanks.
PRANAV SANGHAVI answers, I dont think you should exit from these stocks. You could hold them for a while. If you wisht to exit, it should be on a day when the markets have rallied a good 1000 points.
PRANAV SANGHAVI answers, Although it is a metal sector stock, I think you can hold for a while.
BULL asked, CAN I BUY HDFC BANK AT 930 LEVELS ?
PRANAV SANGHAVI answers, I like the bank but I would wait for it to correct further due to the rising interest rate scenario in the short term may affect the bank.
mandar asked, I am having suzlon at an average price of 1100.Now its quoting around 960+ levels? should I buy more to average the price or should I hold on? can you tell me when can it reach these levels again?
PRANAV SANGHAVI answers, You could hold on.
PRANAV SANGHAVI answers, Looks negative for atleast 2 to 3 more quarters.
PRANAV SANGHAVI answers, I would wait for further corrections.
rohit asked, pls give your take on L&T? What could be the target say in one year?
PRANAV SANGHAVI answers, It is a fundamentally strong stock and can be bought with a 1 to 3 year outlook surely. But buy in parts on dips.
Deepak_007 asked, Hi Pranav. Can you please tell me your views on HLL, M&M, and ITC?
PRANAV SANGHAVI answers, Hi Deepak, HLL is a large FMCG player but gave weak results over the last quarter. So I would watch it for another 1 to 2 quarters. M&M can be bought in to on dips. And also ITC.
ANJAN asked, Dear sir,i am holding gv flims 100 share @7.07 nagarjuna fert. 80 share @ 15.25, Ginni filament @18. i shall i get ant profit from above three script.
PRANAV SANGHAVI answers, You could hold on the Nagarjuna. I would exit the other two and look at growth stocks.
Sudhir asked, Hi Pranav, I am holding shares of Dena Bank. Recently there was news of Dena Bank would merge with some bank.Considering this what would be the future prospect of shares? what is the best price to buy and to sell?
PRANAV SANGHAVI answers, Hi Sudhir, I would look at banking stocks a bit skeptically atleast in the near future. If you wish to look at stocks, I would go for the frontline fundamentally stronger banks.
sarith asked, I have subscribed to the following MF's PRU ICICI FUSION FUND 2 SBI TAX GAIN HDFC TAX SAVER FUND PRU ICICI Emerging Star fund. all for Rs 5000 do you have any sugession for me to balance my portfolio?
PRANAV SANGHAVI answers, You could look at certain bond funds to hedge against the equity funds.
PRANAV SANGHAVI answers, Hold with a long term outlook.
vdatar111 asked, SIR, Seamec locked in upper circuit today any news?
PRANAV SANGHAVI answers, I dont' follow that stock so I woudn't be able to help you.
ramb asked, which stocks in the infrastructure segment are recommended for a 1-2 yr horizon?
PRANAV SANGHAVI answers, I would look at IVRCL, Unitech etc but not at the current moment.
PRANAV SANGHAVI answers, Yes you could.
PRANAV SANGHAVI answers, Mindtree can be held for a while. Lanco I don't follow.
PRANAV SANGHAVI answers, Both are equally efficient ways to invest Gold without paying a premium or taxes.
ANJAN asked, i have hindalco 50 shares. can you tell recently company has announced any transfer of eq. share to pref. share. is it possible without my permission. if it can what will be the ratio.
PRANAV SANGHAVI answers, They must've sent you an intimation with a time deadline after which they are able to convert.
Navin asked, SUggestion about IFCI buy/hold/sell? thnx.
PRANAV SANGHAVI answers, I would get into at levels below 28 and you could hold on for a short term of 3 months.
vijay asked, I hv 200 India cements @188. What shoud I do?
PRANAV SANGHAVI answers, At the current moment the cement sector looks weak especially with the goverment behind them to reduce prices.
rk asked, i have 100 shares of indian bank.Should i sell or hold ?
PRANAV SANGHAVI answers, i would exit on a rally.
PRANAV SANGHAVI answers, You could easily geta 50 % return over that time period.
Shashwath asked, Hello sir, What u suggest about Ranbaxy and Tata tea?Is it time to invest in Tra Stocks?
PRANAV SANGHAVI answers, I would stay out of Ranbaxy and Tata Tea at the current moment.
PRANAV SANGHAVI answers, I wouldn't panic and sell. I think if you hold for 3 months you should see your purchase rate.
lucky asked, i have 200 bharti televentures purchased at the time of IPO?should i retain?
sanpkd asked, what is the future of Reliance Capital. I hold some stocks @685. Should I hold or sell.?
PRANAV SANGHAVI answers, I think you can hold if you are a long term player.
era asked, i bought @500 of polyplex corporation..can you suggest any recommendation for buy/sell?
PRANAV SANGHAVI answers, I would switch to a frontline growth stock.
vijay asked, What is your view on Petronet LNG. Pls reply.
PRANAV SANGHAVI answers, For a longer term it is a hold.
POONAM asked, SHORT TERM WHAT ?
PRANAV SANGHAVI answers, Short term markets should remain volatile.
PRANAV SANGHAVI says, Well it's time for me to leave. Hope to see you'll next week. Bye.
Chat with Pranav every week!


text:
```js
wrex.slice(array, begin[, end])
```
returns a shallow copy of a portion of an array into a new array object.

**array: Array**
* array-like object to slice.

**begin: Integer**
* zero-based index at which to begin extraction.
* As a negative index, begin indicates an offset from the end of the sequence.
* slice(-2) extracts the last two elements in the sequence.
* If begin is omitted, slice begins from index 0.

**end: Integer**
* Zero-based index at which to end extraction. slice extracts up to but not including end.
* (slice(1,4) extracts the second element through the fourth element (elements indexed 1, 2, and 3).
* As a negative index, end indicates an offset from the end of the sequence. slice(2,-1) extracts the third element through the second-to-last element in the sequence.
* If end is omitted, slice extracts to the end of the sequence.

## Examples

### Convert function arguments to an Array
```js
function log() {
  var args = wrex.slice(arguments);
  console.log.apply(console, args);
}
```

redpajama_set_name: RedPajamaGithub


New Discovery Bible School: The Austin South Seventh-day Adventist Church has a very active Bible school that does correspondence Bible lessons with offenders in prisons in Texas as well as in other states. Our church members are involved in mailing the lessons to offenders and grading them. Some of our teachers have developed more personal relationships with offenders by corresponding with them. We use the NewDiscovery Bible lessons developed by the Texas Conference of Seventh-day Adventists specifically designed to be used in the prisons. These lessons are very simple and use fill-in-the blank Bible verses to help offenders learn to know Jesus as their personal Savior and to understand basic Bible truth. These lessons have been an incredible blessing and have led many offenders to surrender their lives to Jesus through a personal decision and through baptism (when available in the prison). Please contact the Austin South Seventh-day Adventist Church for more information regarding our New Discovery Bible School and how it operates.
New Discovery Bible Lessons: The headquarters of New Discovery Bible School, located in Keene, Texas, provides Bible studies to Bible schools who in turn distribute thousands of Bible studies all over the United States. Additional information on starting your own New Discovery Bible School and using these Bible lessons is available at newdiscoverybibleschools.org or New Discovery Bible Schools, Inc., P.O. Box 614, Keene, TX 76059, Phone: 817-760-2222.
Light 4 Learners Bible Lessons by Young Disciple Ministries are used in both our New Discovery Bible School and in our LAMB and Knitting Hearts Together with Jesus Programs. These are truly "one-of-a-kind" Bible lessons. Offenders incarcerated in several prisons have stated that they are "the best-of-the-best" Bible lessons that come into the prison. These lessons spread by word of mouth, with other inmates seeing them and requesting studies for themselves. Light 4 Learner Bible lessons teach the practical of "How do I live a Christian life?" through the Steps to Christ, The Power of Prayer, and Absolute Surrender. Young Disciple Ministries is currently reformatting (to be available in the future) their other Bible lessons for prison offenders: Christ Parables, Jesus' Sermon on the Mount, Pictures of Jesus from His birth to His ascension to Heaven, etc. These lessons are also rich with practical Bible instruction on how God changes us and how He wants us to live. The lessons are colorful and attractive; they contain three levels of challenge: simple fill-in-the-blank Bible verses, a "Study for Yourself" section, and a "Dig Deeper" section; and they have mind challenging puzzles which help think through and apply the concepts taught in the lessons.


Even without having their own greatest individual, the specific Portland Piste Blazers basically verified they may be nonetheless end up being dangerous about the home floors.
Success vacationing remains an additional really make a difference, despite the fact that they will enter Sunday nights matchup with the Sacramento Nobleman from very easily their unique numerous amazing effectiveness using the season.
Despite Damian Lillard lacking 1 / 3 correct gaming, the specific calm Blazers nevertheless concentrated Hard anodized cookware Conference-leading Cleveland regarding similarly concludes to return out of your vacation break utilizing a resounding 105-76 achievement.Noah Vonleh Jersey Portland's numerous lopsided obtain using the season stopped any kind of five-game skid recommended the optimum by simply Wednesday's 26-point harm along with 10-20 Clean Orleans.
Allen Crabbe compensated concerning Lillard's lack utilizing a career-high 26 products, which include twenty one years of age within the preliminary 50 % because Portland (12-20) produced any kind of asking for 63-34 immediate.Al-Farouq Aminu Jersey Contractor Plumlee additional 11 products as well as eighteen rebounds to assist the specific Piste Blazers record any kind of 44-24 products advantage within the colour as well as assistance the actual Cavaliers, coming from the down and dirty Vacation Night harm along with Wonderful Convey, every single child thirty-six.Clyde Drexler Jersey a few percentage shooting.
Portland these days attempts to keep by which unparalleled power for that route, by which it truly is lost a number of correct as well as 13 concerning associated with 16 utilizing a 2-1 begin.
The procedure won't be easy, particularly if Lillard nevertheless seriously isn't prepared to return out of your nagging plantar fasciitis accidental injuries.


License: Canada (Kahnawake), Costa Rica, United Kingdom.
Software: Bodog, MicroPower, RealTime Gaming.
Features: Mobile, Play for Free, Telephone Wagering.
Payment Via: ACH / Electronic Check, Bank Draft, FirePay, MasterCard, Money Order, myCitadel, NETeller, Personal Check, Visa.
Games: 3 Card Poker, Baccarat, Blackjack, Caribbean Stud Poker, Craps, Keno, Let It Ride, Multiplayer Poker, Pai Gow, Racetracks, Red Dog, Roulette, Slot Machines, Sportsbook, Video Poker, War.
Bonus Offers: First time: 10% match from $20-$10000 max. Wow!
All payouts are processed within 24 hours.


text:
Innovative Nigerian Company BudgIT Receives $400K From Omidyar Network
In Companies
ENTERPRISE54 – Omidyar Network announced today a grant of up to $400,000 to BudgIT, a Lagos-based public budget communication startup that promotes civic participation and fiscal transparency in Nigeria. Founded by Oluseun Onigbinde who recently got a nomination for young business leader of the year at the All Africa Business Leaders Award, BudgIT works to
ENTERPRISE54 – Omidyar Network announced today a grant of up to $400,000 to BudgIT, a Lagos-based public budget communication startup that promotes civic participation and fiscal transparency in Nigeria.
Founded by Oluseun Onigbinde who recently got a nomination for young business leader of the year at the All Africa Business Leaders Award, BudgIT works to ensure that Nigerian citizens can exercise their right to access government data by providing the information in a usable format and providing tools that enable constructive debate about the use of public resources.
The two-year grant will be used to expand the amount of budget and procurement information available to the public, stimulate its use in participatory governance, and promote media awareness of open-source tools available to aid in the reporting about public budgets, procurement, and spending.
"Greater transparency of budget, procurement, and spending data will lead to greater government accountability and serve as a deterrent to corruption," said Ory Okolloh, director, investments, Omidyar Network. "BudgIT plays a vital role in enabling access and use of such critical information and fostering greater participatory governance. Omidyar Network is proud to support BudgIT and its mission."
The idea for BudgIT was conceptualized during the February 2011 Tech-In-Governance event, a 48-hour gathering organized by the Co-Creation Hub, another Omidyar Network grantee in Lagos. Since it's launch, BudgIT's website has been visited by hundreds of thousands of unique visitors, and the organization has fielded more than 4,000 requests for data requests and produced more than 60 infographics created to simplify public data for citizens. Its work led Forbes to recognize it as one of the top five African startups to watch in 2013.
Omidyar Network's grant comes through the philanthropic investment firm's Government Transparency initiative, which works to build stronger and more open societies by increasing government responsiveness and citizen participation.
Omidyar Network is a philanthropic investment firm dedicated to harnessing the power of markets to create opportunity for people to improve their lives. Established in 2004 by eBay founder Pierre Omidyar and his wife Pam, the organization invests in and helps scale innovative organizations to catalyze economic and social change. Omidyar Network has committed more than $709 million to for-profit companies and non-profit organizations that foster economic advancement and encourage individual participation across multiple initiatives, including Consumer Internet & Mobile, Education, Financial Inclusion, Government Transparency, and Property Rights.
African Entrepreneurs
BudgIT
Entrepreneurship in Africa
Nigerian entrepreneurs
Oluseun Onigbinde
success stories of Nigerian entrepreneurs
Telema
Now this is just what we're talking about. And it can only better. Congrats Seun!

redpajama_set_name: RedPajamaCommonCrawl


BRCA1/2 pathogenic (P) and likely pathogenic (LP) germline variants are frequent among patients with ovarian carcinoma. However, these variants have not been extensively characterized in patients with ovarian cancer in Brazil.
In this retrospective study we evaluated clinical characteristics and BRCA1/2 genetic test results from patients with ovarian carcinoma who underwent genetic counseling at A.C.Camargo Cancer Center (Brazil) between 2015 and 2017 and had performed germline genetic testing of BRCA1/2 genes.
Among 158 patients, 33 P and LP variants and were found (20.8%), 27 in BRCA1 and six in BRCA2, and six variants of unknown clinical significance (VUS). Thirteen percent of the patients did not have Multiplex Ligation-dependent Probe Amplification (MLPA) results. Three P variants in BRCA1 were found in more than one patient: c.5266dupC (p.Gln1756Profs*74), c.3331_3334delCAAG (p.Gln1111Asnfs5*), and c.211A > G (p.Arg71Gly). One LP variant in BRCA1 had not been previously described, c.4153_4154delCT (p.Leu1385Ilefs*5). Patients with previous diagnosis of breast cancer were carriers of P or LP variant in 8 of 12 cases (66.7%), and patients with a family history of ovarian or breast cancer in first- or second-degree relatives were carriers of P or LP variant in 26.7% of cases compared to 16.9% for patients without family history (p = 0.166).
Prevalence of BRCA1/2 germline P and LP variants is slightly higher than previously described by the largest occidental studies, with a high prevalence of variant c.5266dupC (p.Gln1756Profs*74) in BRCA1 observed. Moreover, we identified a new LP variant.
Ovarian cancer is the most lethal gynecological cancer. In the United States, 22,240 new cases and 14,070 deaths due to ovarian cancer are expected, making it as the 5th most lethal cancer among women . In Brazil, 6150 new cases are expected in 2018 . The high lethality is partially due to diagnosis of the disease in its advanced disease stages in most cases. Even if screening can lead to small benefits in selected high risk groups [3, 4] there is still an unmet need for early diagnosis strategies.
Hereditary Breast and Ovarian Cancer Syndrome (HBOC) occur most often in the presence of germline BRCA1 or BRCA2 pathogenic variants. Carriers of BRCA1 and BRCA2 pathogenic variants have a risk of developing ovarian cancer about 45 and 20% until 80 years old, respectively . Risk-reducing salpingo-oophorectomy decreases the incidence and mortality due to ovarian cancer in this high risk group . Moreover, in the last decade the emergence of PARP inhibitors expanded the importance of BRCA pathogenic variants detection not only to prevention but also to treatment of ovarian cancer patients [7–9].
Earlier studies evaluating exclusively ovarian cancer patients found a frequency of 11 to 15% germline pathogenic variants in BRCA1 or BRCA2 among epithelial ovarian cancer patients [10–15]. The ovarian cancer TCGA confirmed a frequency of 17% germline pathogenic variants in BRCA1 or BRCA2 in 489 unselected ovarian cancer cases . More recent studies in populations from different countries showed a wider range of frequency of pathogenic variants in BRCA1 or BRCA2 depending on the study, with the highest frequencies found in Asian populations reaching 27% of ovarian cancer patients [17–23].
Germline pathogenic variants in other genes related to homologous recombination pathway have also been associated with hereditary ovarian cancer such as PALB2, RAD51C and RAD51D, and are found in about 3 to 5% of ovarian cancer patients [18, 24].
To the best of our knowledge there is only one study that did a comprehensive evaluation of BRCA1 and BRCA2 variants in 100 ovarian cancer patients in Brazil and found a frequency of 19% of pathogenic variants . On the other hand, a second study evaluating only five specific variants in BRCA1 and three in BRCA2 in 103 patients found no pathogenic variants .
Since 2014, BRCA germline testing has been done routinely after genetic counseling at our institution for epithelial ovarian cancer patients. The aim of the present study is to evaluate the frequency of pathogenic and likely pathogenic variants in BRCA1 and BRCA2 among epithelial ovarian cancer Brazilian patients and compare clinical features of BRCA1/2 carriers and non-carriers.
It is a retrospective cohort study including all consecutive patients with ovarian carcinoma tested for BRCA1 and BRCA2 germline mutations seen for genetic counseling in the Oncogenetics Department at A.C. Camargo Cancer Center from January 2015 to November 2017 irrespective o the date of diagnosis (Fig. 1).
All patients included in the study went through genetic counseling consultation at the Oncogenetics Department. Patients were referred to germline BRCA1 and BRCA2 genetic testing, which was performed in different commercial laboratories. Data on identified variants were retrieved from genetic test reports. Patients who presented no pathogenic or likely pathogenic variants in BRCA1 or BRCA2 were routinely recommended to follow the investigation looking for copy number alterations with MLPA. Patients without MLPA results were not excluded from the study.
All pathogenic and likely pathogenic variants and variants of uncertain significance reported by commercial laboratories were reviewed at the Genomics and Molecular Biology Laboratory at A.C. Camargo Cancer Center and reclassified according to the American College of Medical Genetics (ACMG) guidelines in a five tier classification: 1 = benign (B); 2 = likely benign (LB); 3 = variant of unknown significance (VUS); 4 = likely pathogenic (LP); 5 = pathogenic(P) .
Clinical findings were retrieved from the medical records. Baseline characteristics included date of diagnosis, age at diagnosis of ovarian cancer, tumor histological subtype, staging, personal history of ovarian and breast cancer, pretreatment CA125 level. Family pedigrees were reviewed to identify family history of ovarian or breast cancer.
Data on treatment and follow up from the diagnosis until the last date of consultation at the hospital were also retrieved and included: primary versus interval debulking surgery, date of surgery, residual disease, chemotherapy used at first-line treatment, date of last platinum infusion at first-line treatment, response to chemotherapy, date of first recurrence. Data on recurrences included: treatment with secondary debulking surgery, chemotherapy used, date of first and last chemotherapy infusion, response to chemotherapy, and date of disease progression.
Recurrence was defined according to the GCIG (Gynecological Cancer Intergroup) criteria after the analysis of RECIST (Response Evaluation Criteria in Solid Tumors) and CA125 progression was obtained from the medical records. The date of the earlier event was considered for progression [28, 29]. The recurrence detected after 6 months of the last platinum infusion was defined as platinum sensitive recurrence. The recurrence detected within less than 6 months after the last platinum infusion was defined as platinum resistant recurrence. All recurrences that followed this first platinum resistant recurrence were also considered as platinum resistant. Progression-free survival (PFS) was defined as the interval between the date of diagnosis and disease progression or death by any cause. Overall survival (OS) was defined as the interval between the dates of diagnosis and death by any cause. The interval between the date of the last platinum compound infusion and the date of the disease progression was defined as platinum-free interval (PFI).
Response to platinum retreatment data was retrieved from the medical records, and revised for clinical findings, data of CA125 levels and image reports were also collected. GCIG criteria were used to evaluate RECIST and CA125 response [28, 29]. In accordance, each case was categorized as having "response" (complete or partial response) or "no response" (stable disease or disease progression).
Statistical analyzes were performed using the SPSS (v. 21.0; SPSS, Chicago, IL, USA) software, adopting a two-tailed P < 0.05 value as significant.
Frequencies, medians and interquartile range (IQR) were used to describe patients' characteristics and genetic test findings.
The associations between clinical characteristics and response rate to chemotherapy with presence of pathogenic or likely pathogenic variants were investigated using Qui-square test or Fisher's Exact test when necessary.
Overall survival and progression free survival analyses were performed using Kaplan-Meier, log rank test, and hazard ratios were calculated with cox regression analysis.
One hundred and fifty-eight patients were included. Median age was 54.7 years (IQR = 43.1 years to 67.7 years), 70.3% presented high grade serous carcinoma (HGSC), 23.3% presented at FIGO stages I or II and 80.7% presented at FIGO stages III or IV. Baseline clinical characteristics are described in Table 1 according to the final mutational status.
Median time from diagnosis of ovarian cancer to genetic testing was 21.6 months (IQR 10.3 months to 44.5 months). Most patients (53.2%) were tested after first line treatment and before first recurrence, 32.9% were tested in the platinum sensitive recurrent setting, and 8.9% were tested in the platinum resistant setting. Only 21 patients (13.3%) did not have MLPA results available.
Forty-five variants classified as P, LP or VUS were identified among the 158 tested patients according to commercial laboratories reports. After reviewing and reclassifying all P, LP variants and VUS according to ACMG Guidelines we found conflicting interpretation in 8 variants. In BRCA1, the variant c.67_75delGAGTGTCCC (p.Glu23_Pro25del) first classified as VUS was reclassified as LP, based on experimental analysis of three tumors from this patient that showed loss-of-heterozygosity for the normal BRCA1 allele (data not shown). The variant c.4964C > T (p.Ser1655Phe) first classified as P was reclassified as LP, the variant c.2368A > G (p.Thr790Ala) and c.1067A > G (p.Gln356Arg) both first classified as VUS were reclassified as LB and B respectively. In BRCA2 the variants c.794-22C > T, c.7601A > G (p.Ala2534Val), c.1792A > G (p.Thr598Ala), and c.4928 T > C (p.Val1643Ala), first classified as VUS were all reclassified as LB.
After reclassification there were 33 P or LP variants, representing a frequency of 20.8%, 27 in BRCA1 and six in BRCA2, and six VUS, three in BRCA1 and three in BRCA2. One of the 33 P or LP variants was a large deletion of exon 16 in BRCA1. All variants first classified as P, LP or VUS according to commercial laboratories are described in Table 2 according to their reclassification status.
Three variants were found in more than one patient, all in BRCA1: the Ashkenazi founder mutation c.5266dupC (p.Gln1756Profs*74) was found in five patients. One of the five patients carrying this variant had a recognized Jewish ancestry; the variant c.3331_3334delCAAG (p.Gln1111Asnfs5*) was found in three patients; and the variant c.211A > G (p.Arg71Gly) was found in two patients.
One LP variant in BRCA1 has not been described before in Brazilian patients, nor in any consulted public databases (Clinvar, BIC and LOVD) c.4153_4154delCT (p.Leu1385Ilefs*5).
Median age at diagnosis and median time from diagnosis to genetic testing was not different between P and LP variant carriers and non-carriers. FIGO stage and CA125 baseline levels were also not different between P and LP variant carriers and non-carriers (Table 1).
Patients with high grade serous carcinoma were found to carry a P or LP variant in 24.5% of cases compared to 13.0% for other histological subtypes (p = 0.105). Among histological subtypes other than HGSC, P or LP variants were found in one endometrioid tumor, one low grade serous carcinoma, two undifferentiated carcinomas and two carcinosarcomas. Patients with previous diagnosis of breast cancer were found to carry a P or LP variant in 8 of 12 cases (66.7%) compared to 18.0% for patients without previous history of breast cancer (p = 0.001). Patients with family history of ovarian or breast cancer in first or second degree relatives were found to carry a P or LP variant in 26.7% of cases compared to 16.9% for patients without previous history of family history of ovarian or breast cancer (p = 0.166). According to the time point genetic testing was taken, patients tested at the first line, platinum sensitive and platinum resistant settings were found to carry P or LP variants in 22.6, 21.2 and 7.1% of cases respectively (p = 0.493) (Fig. 2).
Clinical endpoints indicating better prognosis and greater sensitivity to platinum therapy were not different according to P or LP carrier status. With a median follow-up time since diagnosis of 63.0 months, estimated median OS for all patients was 110.9 months and median PFS after first line treatment was 19.6 months. Comparing P and LP carriers with non-carriers, median OS was 122.8 months versus 110.9 months (p = 0.971) with a HR = 1.01 (95%CI 0.55–1.88; p = 0.971), and median PFS was 17.3 versus 20.8 months (p = 0.997) with a HR = 1.04 (95%CI 0.64–1.69; p = 0.889). First recurrence was classified as platinum sensitive in 75.0% versus 70.0% of cases (p = 0.876) and second recurrence after first platinum sensitive recurrence was classified as platinum sensitive in 72.7% versus 59.4% of cases (p = 0.494) (Fig. 3).
This is the largest series evaluating germline BRCA1 and BRCA2 with comprehensive gene analysis in a Brazilian population of ovarian cancer patients. We found a frequency of 17.1% of P and LP variants in BRCA1, 3.7% in BRCA2, and 3.7% of VUS considering both genes. Frequency and type of BRCA pathogenic variants among ovarian cancer patients varies according to the studied populations. Most European and US studies have shown frequencies between 11 and 17% [10–13, 15, 23]. One recent German study found a slightly higher frequency of BRCA pathogenic variants of 20% . Studies from non-European or US populations showed higher frequencies, with 23% in Korean patients [21, 31], 27% in Chinese patients [19, 20] and 29% in Arabic patients . Our findings put the frequency of pathogenic variants in BRCA in Brazilian ovarian patients on the upper frequency range of European and US studies. One previous study in Colombian patients found a frequency of 15%  and one previous Brazilian study found a frequency of 19% . All these studies did comprehensive sequencing of BRCA1 and BRCA2.
We included only patients that were referred to genetic counseling, this could lead to a selection bias because patients who are referred to genetic counseling could be those who have a more suspicious family history. Indeed, only 41% of our patients had no history of breast or ovarian cancer or personal history of breast cancer. This selection bias could be one of the reasons of the higher prevalence found in our study.
Three pathogenic variants in BRCA1, c.5266dupC (p.Gln1756Profs*74), c.3331_3334delCAAG (p.Gln1111Asnfs5*), and c.211A > G (p.Arg71Gly) were found more than once. The variant c.5266dupC (p.Gln1756Profs*74) is an Ashkenazi founder mutation that has already been described as a frequent variant in Brazilian patients with Hereditary Breast and Ovarian Cancer Syndrome [25, 32]. The variant c.3331_3334delCAAG (p.Gln1111Asnfs5*) is probably originated in Spain and has also been previously described as a frequent variant in ovarian cancer patients in Brazil and Latin America . The variant c.211A > G (p.Arg71Gly) is a missense variant in the second-last position of the donor splice site of exon 5, which was proved to interfere in the splicing of this exon and results in a deletion of 22 bp of exon five, creating with the first bases of exon 6 a termination codon at position 64 . It is a Spanish founder mutation and has been described in Latin American patients and, to a lesser extent, in Brazilian patients [33, 34].
One LP variant in BRCA1 has not been described before c.4153_4154delCT (p.Leu1385Ilefs*5). It is a frameshift variant that leads to a premature stop codon and for these reason was classified as LP variant according to ACMG Guidelines .
Four variants in BRCA1 and four variants in BRCA2 had conflicting interpretation when reviewed at our institution in comparison to commercial laboratories reports, a frequency of 17.7% disagreement. Balmaña et al. reported discrepancies on variant interpretation among laboratories to be as high as 27% . As expected, seven of the eight variants with conflicting interpretation were missense variants, and six of eight presented discordances between VUS and B or LB calls that would not have changed clinical management. Besides, 13% of patients did not have results on MLPA. The possibility of misinterpreted variants as non P or LP by commercial laboratories and the absence of MLPA results for 13% of patients may have led to an underestimation of BRCA P or LP variants in our study.
In accordance with previous studies, high frequency of BRCA1 and BRCA2 P or LP variants was present even in the subgroups with the lowest rates, for instance patients with no family history of breast or ovarian cancer and no previous breast cancer had P or LP variants in 16.9% of cases, justifying genetic testing for all patients . The highest frequency was found among women with previous breast cancer, who had a chance of 66.7% of carrying P or LP variants in BRCA1 or BRCA2. Patients with platinum sensitive relapse showed the same odds of carrying P or LP variants as patients after primary treatment, and patients with platinum resistant relapse showed P or LP variants in 7.1%. The smaller frequency of P and LP variants among patients tested at the platinum resistant scenario could be explained by the higher sensibility of BRCA mutated tumors to platinum therapy, and has also been described before . We did not find a longer progression free or overall survival for P and LP carriers, but the small number of patients in the study and the number of deaths lower than expected for ovarian cancer patients hampers any conclusion on this regard. The small number of death events may be due to a not long enough follow-up time and the selection bias present in the study since patients diagnosed before 2015 were included if they were seen in the Oncogenetics department after 2015.
In conclusion, we confirmed a frequency of P and LP variants in BRCA1 and BRCA2 in patients with ovarian carcinoma slightly above the expected for European and US populations but smaller than shown by Asian studies, demonstrating the specific genetic characteristics of Brazilian ovarian cancer patients who present a high frequency of the c.5266dupC (p.Gln1756Profs*74) variant and one not previously described variant.
We acknowledge Misses Gisleine Nieto for the support with the paperwork.
We had no financial support.
DBP, AABAC conceived and designed the study. ARGR NCP, CC, CCCM, DP, DCQS, RJ, HM, GB and MNF contributed with clinical data acquisition, analysis and interpretation. GTT and DMC analyzed and reclassified genomic variants in genetic reports. GB and LB contributed with loss of heterozigosity analysis in the tumor samples. AABAC performed the statistical analysis. AABAC and DBP wrote and edited the manuscript. All authors read and approved the final version of the manuscript.
The A.C. Camargo Cancer Center Ethics Committee approved the study (CEP# 2450/17). The need for informed consent has been waived by the A.C. Camargo Cancer Center Ethics Committee.


Prior to the upcoming AGM (you should have received a notification via e-mail) membership numbers are looking good. We currently have 827 members with quite a few renewals still to arrive. When you do renew your membership please make sure you send us the Renewal Form. We need this form to track your renewal through the renewal process, especially as the renewal is processed by 2 people in different states. Well done to those who renewed recently.


13 out of 23 customers would recommend this product to a friend.
Infused with skin-essential minerals and a plant extract, our Kind to Skin+ Eye Pads formulation effectively cleanses your eyes of make-up (including waterproof mascara) and impurities whilst instantly hydrating the skin around your eyes – making them perfect for sensitive, dehydrated or dry skin.
Cleansing plays an important part in a healthy skincare regime. However some eye- make-up removers are harsh and can strip away natural oils, making the skin around your eyes feel tight, dry and dehydrated. Simple Kind to Skin+ Eye Pads are infused with skin-essential minerals and do not contain harsh chemicals, artificial colours or perfume, making them perfectly suitable for dehydrated, dry or sensitive skin.
Simple Kind to Skin+ Eye Pads are part of the Simple Kind to Skin+ skincare range. Why not try out our other products in the Simple Kind to Skin+ range to help keep your skin extra soft and cleansed? After using with Simple Kind to Skin+ Eye Pads, we recommend cleansing your face with Simple Water Boost Micellar Facial Gel Wash. Finish with by smoothing Simple Hydrating Gel Cream into your face and neck to instantly moisturise your skin and complete your hydration skincare routine.
For specially designed cleansers which are kind to eyes, make sure to check out our Simple eye balm, eye cream and eye roll on!
I don't wear much make-up but this did a good job of removing eye make up and mascara. Handy pads as well.
Does not remove waterproof mascara. Not a fan!
I thought these remover pads would be perfect. A tiny size, effective and great for travel and would save taking my usual trusty but bulky bottle of remover. Unfortunately, I struggled with one pad to remove my mascara (one light coat) and had to use several. They just weren't up to the job and really made my eyes sting. I didn't think that would happen with a 'Simple' product.
Removes standard mascara and eyeshadow as thats what Im usually wearing. Nice, moist and doesnt irritate. Star less for the price (£4) but really handy to take away on a holiday.
Wore waterproof mascara, eyeliner and eyeshadow and these wipes did the job as promised! Used a wipe per eye, and found it got rid of all the makeup and caused no irritation to my skin which is dry and sensitive.
Did a pretty good job, and very gentle on the skin but I don't wear a huge amount of eye make up... not sure how they'd manage a more heavily made up eye!


text:
Legal Operations » Third Fine for Meta in 2022 Is One of Highest GDPR Penalties
Third Fine for Meta in 2022 Is One of Highest GDPR Penalties
Meta Platforms Inc. was hit with a $277 million fine for failing to prevent the leak of the personal data of more than half a billion users of its Facebook service. The Irish Data Protection Commission (DPC) levied the fine following a probe that found Meta had failed to apply the strict safeguards required under the General Data Protection Regulation (GDPR). On top of the fine, the third-biggest under the GDPR, the DPC ordered Meta's Irish unit to ensure its processing complies with the law. The DPC opened its probe following revelations that "a collated dataset of Facebook personal data" had been published on the internet. Personal information on 533 million Facebook users worldwide reemerged on a hacker website last year, including their birthdates, phone numbers, locations and email addresses. The investigation looked into Facebook Search, Facebook Messenger Contact Importer and Instagram Contact Importer tools with regard to Meta's processing between May 2018 and September 2019. The social network previously said that the data was old and the problem had been fixed in 2019. This is the third fine the DPC has imposed on Meta this year, with the total reaching nearly $700 million.
← In-House Attorneys' Role In Addressing Corporate Sector's Reputation
Automated Workflows Improve Client Relationships and Matter Progression →


text:
#pragma once
#include "IConfig.h"

namespace Wuild {
class InvocationToolConfig : public IConfig {
public:
    static const std::string VERSION_NO_CHECK;

public:
    struct Tool {
        enum class ToolchainType
        {
            GCC,
            MSVC,
            Clang,
            UpdateFile,
            AutoDetect,
        };

        std::string              m_id;
        std::string              m_removeRemote;
        std::string              m_appendRemote;
        std::string              m_remoteAlias;
        std::string              m_version;
        ToolchainType            m_type = ToolchainType::AutoDetect;
        std::vector<std::string> m_names;
    };
    std::vector<Tool> m_tools;
    StringVector      m_toolIds;

    std::string GetFirstToolId() const;
    std::string GetFirstToolName() const;
    bool        Validate(std::ostream* errStream = nullptr) const override;
    std::string Dump() const;
};
}