The role of the exit in the initial screening of investment opportunities: The case of business angel syndicate gatekeepers

The exit process has been largely ignored in business angel research.. The practitioner community identifies the difficulty in achieving exits as the most pressing problem for investors. This has been attributed to the failure of investors to adopt an exit-centric approach to investing. The validity of this claim is examined via a study of the investment approach of 21 ‘gatekeepers’ (managers) of angel groups in Scotland and Northern Ireland. Most gatekeepers say that they do consider the exit when they invest. However, this is contradicted by a verbal protocol analysis which indicates that the exit is not a significant consideration in their initial screening process. The small number of exits achieved by the groups is consistent with the general lack of an exit-centric approach to investing. Only three groups exhibit evidence of a strong exit-centric approach to investing. The lack of exits may have a negative impact on the level of future angel investment activity

Managing the trade-off implications of global supply

The cost versus response trade-off is a growing logistics issue due to many markets being increasingly characterized by demand uncertainty and shorter product life cycles. This is exacerbated further with supply increasingly moving to low cost global sources. However, the poor response implications of global supply are often not addressed or even acknowledged when undertaking such decisions. Consequently, various practical approaches to minimising, postponing or otherwise managing the impact of the demand uncertainty are often only adopted retrospectively. Even though such generic solutions are documented through case examples we lack effective tools and concepts to support the proactive identification and resolution of such trade-offs. This paper reports on case-based theory building research, involving three cases from the UK and USA used in developing a conceptual model with associated tools, in support of such a process

Threshold behavior in metastable dissociation of multi-photon ionized thymine and uracil

Microsecond-timescale HNCO loss has been observed from single-color multi-photon ionized pyrimidine nucleobases in the gas phase. Photon energy thresholds for the metastable channels have been measured at 5.55 ± 0.02 eV for thymine and 5.57 ± 0.02 eV for uracil. We argue that these results can be attributed to accessing the molecules’ S1 states with additional vibrational energy matching the threshold energy for HNCO loss from the radical cation. Combined with previous photoionization energies, this enables the S1 adiabatic energies to be deduced: 3.67 ± 0.07 eV for thymine and 3.77 ± 0.07 eV for uracil. These values are consistent with recent calculations

Prospects for ACT: simulations, power spectrum, and non-Gaussian analysis

A new generation of instruments will reveal the microwave sky at high resolution. We focus on one of these, the Atacama Cosmology Telescope, which probes scales 1000<l<10000, where both primary and secondary anisotropies are important. Including lensing, thermal and kinetic Sunyaev-Zeldovich (SZ) effects, and extragalactic point sources, we simulate the telescope's observations of the CMB in three channels, then extract the power spectra of these components in a multifrequency analysis. We present results for various cases, differing in assumed knowledge of the contaminating point sources. We find that both radio and infrared point sources are important, but can be effectively eliminated from the power spectrum given three (or more) channels and a good understanding of their frequency dependence. However, improper treatment of the scatter in the point source frequency dependence relation may introduce a large systematic bias. Even if all thermal SZ and point source effects are eliminated, the kinetic SZ effect remains and corrupts measurements of the primordial slope and amplitude on small scales. We discuss the non-Gaussianity of the one-point probability distribution function as a way to constrain the kinetic SZ effect, and we develop a method for distinguishing this effect from the CMB in a window where they overlap. This method provides an independent constraint on the variance of the CMB in that window and is complementary to the power spectrum analysis.Comment: 22 pages, 11 figures. Submitted to New Astronomy. High resolution figures provided at http://www.princeton.edu/~khuffenb/pubs/prospects-act.htm

Truncated and Helix-Constrained Peptides with High Affinity and Specificity for the cFos Coiled-Coil of AP-1

Protein-based therapeutics feature large interacting surfaces. Protein folding endows structural stability to localised surface epitopes, imparting high affinity and target specificity upon interactions with binding partners. However, short synthetic peptides with sequences corresponding to such protein epitopes are unstructured in water and promiscuously bind to proteins with low affinity and specificity. Here we combine structural stability and target specificity of proteins, with low cost and rapid synthesis of small molecules, towards meeting the significant challenge of binding coiled coil proteins in transcriptional regulation. By iteratively truncating a Jun-based peptide from 37 to 22 residues, strategically incorporating i-->i+4 helix-inducing constraints, and positioning unnatural amino acids, we have produced short, water-stable, alpha-helical peptides that bind cFos. A three-dimensional NMR-derived structure for one peptide (24) confirmed a highly stable alpha-helix which was resistant to proteolytic degradation in serum. These short structured peptides are entropically pre-organized for binding with high affinity and specificity to cFos, a key component of the oncogenic transcriptional regulator Activator Protein-1 (AP-1). They competitively antagonized the cJun–cFos coiled-coil interaction. Truncating a Jun-based peptide from 37 to 22 residues decreased the binding enthalpy for cJun by ~9 kcal/mol, but this was compensated by increased conformational entropy (TDS ≤ 7.5 kcal/mol). This study demonstrates that rational design of short peptides constrained by alpha-helical cyclic pentapeptide modules is able to retain parental high helicity, as well as high affinity and specificity for cFos. These are important steps towards small antagonists of the cJun-cFos interaction that mediates gene transcription in cancer and inflammatory diseases

New differential equations for on-shell loop integrals

We present a novel type of differential equations for on-shell loop integrals. The equations are second-order and importantly, they reduce the loop level by one, so that they can be solved iteratively in the loop order. We present several infinite series of integrals satisfying such iterative differential equations. The differential operators we use are best written using momentum twistor space. The use of the latter was advocated in recent papers discussing loop integrals in N=4 super Yang-Mills. One of our motivations is to provide a tool for deriving analytical results for scattering amplitudes in this theory. We show that the integrals needed for planar MHV amplitudes up to two loops can be thought of as deriving from a single master topology. The master integral satisfies our differential equations, and so do most of the reduced integrals. A consequence of the differential equations is that the integrals we discuss are not arbitrarily complicated transcendental functions. For two specific two-loop integrals we give the full analytic solution. The simplicity of the integrals appearing in the scattering amplitudes in planar N=4 super Yang-Mills is strongly suggestive of a relation to the conjectured underlying integrability of the theory. We expect these differential equations to be relevant for all planar MHV and non-MHV amplitudes. We also discuss possible extensions of our method to more general classes of integrals.Comment: 39 pages, 8 figures; v2: typos corrected, definition of harmonic polylogarithms adde

Electronic excitation of carbonyl sulphide (COS) by high-resolution vacuum ultraviolet photoabsorption and electron-impact spectroscopy in the energy region from 4 to 11 eV

The electronic state spectroscopy of carbonyl sulphide, COS, has been investigated using high resolution vacuum ultraviolet photoabsorption spectroscopy and electron energy loss spectroscopy in the energy range of 4.0–10.8 eV. The spectrum reveals several new features not previously reported in the literature. Vibronic structure has been observed, notably in the low energy absorption dipole forbidden band assigned to the (4π←3π) (1Δ←1Σ+) transition, with a new weak transition assigned to (1Σ−←1Σ+) reported here for the first time. The absolute optical oscillator strengths are determined for ground state to 1Σ+ and 1Π transitions. Based on our recent measurements of differential cross sections for the optically allowed (1Σ+ and 1Π) transitions of COS by electron impact, the optical oscillator strength f0 value and integral cross sections (ICSs) are derived by applying a generalized oscillator strength analysis. Subsequently, ICSs predicted by the scaling are confirmed down to 60 eV in the intermediate energy region. The measured absolute photoabsorption cross sections have been used to calculate the photolysis lifetime of carbonyl sulphide in the upper stratosphere (20–50 km)

The thermal SZ tomography

The thermal Sunyaev-Zel'dovich (tSZ) effect directly measures the thermal pressure of free electrons integrated along the line of sight and thus contains valuable information on the thermal history of the universe. However, the redshift information is entangled in the projection along the line of sight. This projection effect severely degrades the power of the tSZ effect to reconstruct the thermal history. We investigate the tSZ tomography technique to recover this otherwise lost redshift information by cross correlating the tSZ effect with galaxies of known redshifts, or alternatively with matter distribution reconstructed from weak lensing tomography. We investigate in detail the 3D distribution of the gas thermal pressure and its relation with the matter distribution, through our adiabatic hydrodynamic simulation and the one with additional gastrophysics including radiative cooling, star formation and supernova feedback. (1) We find a strong correlation between the gas pressure and matter distribution, with a typical cross correlation coefficient r ~ 0.7 at k . 3h/Mpc and z < 2. This tight correlation will enable robust cross correlation measurement between SZ surveys such as Planck, ACT and SPT and lensing surveys such as DES and LSST, at ~20-100{\sigma} level. (2) We propose a tomography technique to convert the measured cross correlation into the contribution from gas in each redshift bin to the tSZ power spectrum. Uncertainties in gastrophysics may affect the reconstruction at ~ 2% level, due to the ~ 1% impact of gastrophysics on r, found in our simulations. However, we find that the same gastrophysics affects the tSZ power spectrum at ~ 40% level, so it is robust to infer the gastrophysics from the reconstructed redshift resolved contribution.Comment: 10 pages, 7 figures, 2 appendices, accepted by Ap

Solution of the structure of tetrameric human glucose 6-phosphate dehydrogenase by molecular replacement

Recombinant human glucose 6-phosphate dehydrogenase (G6PD) has been crystallized and its structure solved by molecular replacement. Crystals of the natural mutant R459L grow under similar conditions in space groups P212121 and C2221 with eight or four 515-residue molecules in the asymmetric unit, respectively. A non-crystallographic 222 tetramer was found in the C2221 crystal form using a 4 A resolution data set and a dimer of the large beta + alpha domains of the Leuconostoc mesenteroides enzyme as a search model. This tetramer was the only successful search model for the P212121 crystal form using data to 3 A. Crystals of the deletion mutant DeltaG6PD grow in space group F222 with a monomer in the asymmetric unit; 2.5 A resolution data have been collected. Comparison of the packing of tetramers in the three space groups suggests that the N-terminal tail of the enzyme prevents crystallization with exact 222 molecular symmetry.published_or_final_versio