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Aging is often perceived as a degenerative process resulting from random accrual of cellular damage over time. Despite this, age can be accurately estimated by epigenetic clocks based on DNA methylation profiles from almost any tissue of the body. Since such pan-tissue epigenetic clocks have been successfully developed for several different species, we hypothesized that one can build pan-mammalian clocks that measure age in all mammalian species. To address this, we generated data using 11,754 methylation arrays, each profiling up to 36 thousand cytosines in highly-conserved stretches of DNA, from 59 tissue-types derived from 185 mammalian species. From these methylation profiles, we constructed three age predictors, each with a single mathematical formula, termed universal pan-mammalian clocks that are accurate in estimating the age (r>0.96) of any mammalian tissue. Deviations between epigenetic age and chronological age relate to mortality risk in humans, mutations that affect the somatotropic axis in mice, and caloric restriction. We characterized specific cytosines, whose methylation levels change with age across most mammalian species. These cytosines are greatly enriched in polycomb repressive complex 2-binding sites, are located in regions that gradually lose chromatin accessibility with age and are proximal to genes that play a role in mammalian development, cancer, human obesity, and human longevity. Collectively, these results support the notion that aging is indeed evolutionarily conserved and coupled to developmental processes across all mammalian species - a notion that was long-debated without the benefit of this new compelling evidence.SUMMARYThis study identifies and characterizes evolutionarily conserved cytosines implicated in the aging process across mammals and establishes pan mammalian epigenetic clocks.

Objectives: Preeclampsia is associated with maternal morbidity and mortality during pregnancy, and also an increased cardiovascular disease (CVD) risk later in life. During preeclampsia, alterations in secreted placental factors leading to systemic maternal endothelial dysfunction are evident. However, little is known about the associated endothelial intracellular signaling. STAT3 is a latent cytoplasmic transcription factor involved in endothelial cell differentiation, survival, and angiogenesis. We aimed to test if preeclampsia and preeclampsia-related placental factors could alter serum-induced STAT3(Y705) activation in endothelial cells. Furthermore, if altered serum-induced endothelial STAT3 (Y705) activation is related to post-preeclamptic CVD risk. Study design: HUVECs were used as a model of maternal endothelium. Experiments entailed addition of 20% human pregnancy serum as well as addition of recombinant PlGF, sFLT1 and VEGF-A165a to the cells. Main outcome measures: Levels of pSTAT3(Y705) related to STAT3 levels were evaluated by immunoblotting analysis. Results: Our results show that preeclamptic serum induces significantly lower STAT3(Y705) phosphorylation compared with uncomplicated pregnancy serum (P = 0.0089) in endothelial cells. Furthermore, STAT3(Y705) phosphorylation was not changed upon addition of PlGF, sFLT1, or VEGF-A165a together with pregnancy sera compared with sera alone. Finally, sera from women with previous preeclampsia and current hypertension and carotid atherosclerotic plaques show significantly lower STAT3(Y705) phosphorylation capabilities compared with healthy women with previous uncomplicated pregnancies 8–18 years after deliveries (P = 0.029). Conclusions: Reduction in serum-induced endothelial STAT3(Y705) activation may play an important role in the preeclampsia-associated endothelial dysfunction. Additionally, reduced endothelial STAT3(Y705) phosphorylation may contribute to increased post-preeclamptic CVD risk 8–18 years after delivery.

Twenty commercially available monoclonal antibodies (mAbs) raised against various human leucocyte surface antigens were tested on lymphocytes, monocytes and granulocytes from horse, pig, cow, sheep, goat, dog, mink, rabbit, rhesus monkey as well as man. Eight antibodies reacted with leucocytes from some of the animals. These were the antibodies against CD2, CD4, CD5, CD8, CD14, CD18, HLA-DR, and the HLA-ABC antigen. The CD18 antibody reacted with lymphocytes, monocytes and granulocytes from all animals tested except goat. The CD14 antibody reacted with monocytes from pig, cow, sheep, goat, dog, mink, rabbit and monkey and with granulocytes from pig and rabbit. The anti-HLA-ABC reacted with leucocytes from monkey and cow. Finally, the CD2, CD4, CD5 and CD8 antibodies reacted with leucocytes from monkey only.

We complete our programme of deriving characters of the N = 4 algebra A γ , containing two SU(2) Kac-Moody subalgebras, by treating the complications arising for massless representations. We find it useful to work directly with the algebra A γ , A γ being the direct sum of that and four free fermions plus a U(1) FM. Only in A γ do massless representations have non-vanishing Witten index. Several consistency checks on our explicit formulas are given.

We derive formulas for the characters of the N = 4 algebra A γ which contains two SU(2) Kac-Moody subalgebras. We present results for unitary, highest weight, massive representations in the Ramond and Neveu-Schwarz sectors. Massive characters are given for the A γ algebra, which is closely related to A γ, with no dimension - 1 2 operators but rather composite operators in the OPE's. Comparison with previously known results in relevant limits are performed.

The structure of the peroxidase from Coprinus cinereus (CiP) has been determined in three different space groups and crystalline environments. Two of these are of the recombinant glycosylated form (rCiP), which crystallized in space groups P2(1)2(1)2(1) and C2. The third crystal form was obtained from a variant of CiP in which the glycosylation sites have been removed (rCiPON). It crystallizes in space group P2(1) with beta approximately 90 degrees; the structure was determined from room-temperature data and low-temperature data obtained from twinned crystals. Two independent molecules of CiP related by non-crystallographic symmetry are contained in the three crystal forms. The packing in the two structures of the glycosylated form of rCiP is closely related, but differs from the packing in the unglycosylated rCiPON. A database search based on small-molecule porphinato iron (III) complexes has been performed and related to observations of the spin states and coordination numbers of the iron ion. The room-temperature structures of CiP and one structure of the almost identical peroxidase from Arthromyces ramosus (ARP) have been used to identify 66 conserved water molecules and to assign a structural role to most of them.

Aims: To examine the hypothesis that lymphatic dissemination in breast cancer occurs sequentially. Methods: Thirty patients with clinically localized adenocarcinoma were studied. Patent blue dye was administered into the tumour at the beginning of a modified radical mastectomy or segmental mastectomy with en bloc axillary lymph-node dissection (ALND). In the removed specimen, blue-stained lymphatic channels were dissected from the primary tumour to the first draining lymph node(s) (sentinel node(s)). Results: Identification of a sentinel node (SN) was successful in 26 patients (87%). In 10 patients the SN was tumour-positive. In six of these patients, the SN was the only tumour-positive node. There was no incidence of ‘skip' metastasis. Conclusions: This study confirms the sequential nature of lymphatic dissemination. When confirmed in vivo , these data may lead to a substantial reduction of the need for ALND without compromising survival and regional control and without loss of prognostic and staging information.

Character sumrules associated with the realization of the $N=4$ superconformal algebra $\At$ on manifolds corresponding to the group cosets $SU(3)_{\ktp }/U(1)$ are derived and developed as an important tool in obtaining the modular properties of $\At$ characters as well as information on certain extensions of that algebra. Their structure strongly suggests the existence of rational conformal field theories with central charges in the range $1 \le c\le 4$. The corresponding characters appear in the massive sector of the sumrules and are completely specified in terms of the characters for the parafermionic theory $SU(3)/(SU(2)\times U(1))$ and in terms of the branching functions of massless $\At$ characters into $SU(2)_{\ktp }\times SU(2)_1$ characters., 31 pages, DTP/92/49 NBI-HE-92-73 (latex file)

Autogeny was much more prevalent in a temperate than in a tropical population of Deinocerites pseudes . Most sugarfed De. pseudes females did not initiate autogenous egg development until after mating. High proportions (>90%) of autogeny were found in tropical, subtropical, and temperate-zone populations of Deinocerites cancer . Either sugar feeding or mating triggered egg development in De. cancer, but sugar-fed females produced more eggs. Whether sugar-fed or not, unmated De. cancer females developed eggs after blood feeding. Thus 3 factors, blood feeding, sugar feeding, or mating, can independently stimulate the production of the initial egg clutch in De. cancer .

We investigate the open fermion string (corresponding to the Neveu-Schwarz-Ramond model) by use of Polyakov's approach to the quantization problem. Supersymmetric boundary conditions on various fields are derived, and the boundary terms due to the superconformal anomaly are computed. It turns out that “supersymmetrization” of one-dimensional boundary terms induces two-dimensional terms.

A previously developed formalism for the bosonic string is extended to the Neveu-Schwarz-Ramond string using 2-d superspace techniques throughout. Three-string vertices for NS and R-strings are constructed, sewing rules developed, and the technique of quasi-superconformal modes is set up for constructing the measure on supermoduli space. Symmetries, such as superconformal invariance and BRST invariance, are guaranteed ab initio. Picture changing and bosonization are avoided. Examples are given. The formalism should allow a superstring loop calculus based on supermoduli. Results concerning the ensuing super-Schottky description are given.

We present a solution for simple curves of the Makeenko-Migdal equation which leads to string dynamics. By the non-renormalized nature of the equation, any formal solution requires some extra physics input before it can be meaningfully interpreted. We then propose a “minimal” renormalization both of the Wilson loop for a large number of colors and of the corresponding Makeenko-Migdal equation. This scheme is based on Witten's idea of a master field. The regularized solution contains a scale (related to the Regge slope) which we connect to a gauge-invariant domain size in the QCD vacuum, and the solution can only make sense for loops that are large relative to this scale. Using a vortex condensate model for the QCD vacuum, the length parameter is related to the QCD length scale.

Single crystal neutron diffraction measurements of K2Pt(CN)4Br0.3 · 3H2O (KCP) above room temperature, to the point of irreversible crystal breakdown (318–323°K), and at liquid nitrogen temperature (77°K), give no indication of a crystallographic phase change. Full three-dimensional data collected at 77°K ( a = 9.848(5) A , c = 5.714(3) A , and space group P4mm ) indicate that the structure is essentially unchanged from that at room temperature except for increased hydrogen bonding association between H2O(2) and Br(1). The possible relationship between the hydrogen bonding changes and Br(1) site ordering is discussed.

The Kac formula for superconformal dimensions (generalized to N = 2) is further developed (compared to a previous article). A list of discrete values of the central charge for which unitary representations are expected to exist is proposed. For several of these, unitarity is checked by computer. For two values, unitarity is proven by providing explicit fermionic representations. For one of those values, the N = 2 theory coincides with a sub theory of one of the known unitary N = 1 theories, thus extending a similar situation between N = 0 and N = 1.

We propose a general definition of a Veneziano-model amplitude in terms of the support property of its double inverse Laplace transform. A practical test of this property is then formulated and applied to ..pi pi.. scattering. It is satisfied by the nonexotic ..pi pi.. amplitudes but not by the exotic ..pi../sup +/..pi../sup +/ scattering amplitude. However there are significant deviations from the explicit Lovelace-Shapiro model and the isovector-exchange amplitude is better represented by the symmtric-group model of Frampton.

We construct in a very simple way a three-reggeon vertex that includes also the contribution of the ghost coordinates, both for the bosonic and fermionic string. We show its connection with the vertex operators that are usually used to construct dual amplitudes and with the light-cone three-string vertex. Finally, we prove its invariance under BRST transformations.

Temephos (Abate1®), applied at a rate calculated to give a concentration of I ppm maintained for 10 min, cleared streams of immature black flies and effectively controlled a pest problem at the Fortuna Hydroelectric Project, Chiriqui Province, Republic of Panama. Simulium quadrivittatum accounted for over 90% of 16,544 simuliids captured on human bait during 1 year (October 1977–September 1978). Simulium metallicum and S. callidum , though primarily zoophilic, were also captured biting humans. Before control, the maximum mean fly density for any month was 53 flies/man-h (June 1976); during peak periods, however, fly densities exceeded 100 flies/man-h. Larvae and pupae of S. quadrivittatum were found most frequently in spring-led trickles of water in pastures. After treatment began in August 1978, adult biting densities decreased from 20 flies/man-h during July 1978 to less than 6 flies/man-h during September 1978. From March 1980 to May 1981, mean monthly densities within the treated area averaged 1.6 ± 0.2 flies/man-h; outside the treated area, fly densities averaged 14.1 ± 1.8 flies/man-h.

We study consequences of defining the impact parameter as being the variable conjugate to transverse relative c.m. momentum, p ⊥ . This coincides with a proposal originally made by Chang and Raman. The dynamical information carried by these are intimately connected to the behaviour of 90° scattering. In particular, impact parameter dynamics is a priori qualitatively different from direct channel angular momentum dynamics. A phenomenological study of elastic π ± p and pp data at fixed values of longitudinal momentum, p ‖ , leads to a generalized geometrical scaling hypothesis. In contrast with the power behaviour predicted by parton models, the data suggest exponential behaviour of the scaling amplitudes at fixed p ‖ of the type e Rp⊥ with R ≅ 1 fm. Correspondingly these amplitudes are described by a pair of complex conjugate singularities on the imaginary axis in the impact parameter plane.

Covariant N-string amplitudes for the closed bosonic string are analyzed with emphasis on the relation between ghost zero modes and integration measure over Koba-Nielsen like variables (here we find that a modification of the results of refs. [1,18] is needed). Factorization and correct BRST-cohomology properties are established. Multi-loop amplitudes for arbitrary external states are constructed by formulating sewing rules generalizing the old treatment of reggeons to include ghosts. In particular the ghost zero modes encode and generate the measure on moduli space in a way similar to ideas proposed by Martinec [2]. Explicit N-tachyon multi-loop results agree with results of ref. [30] obtained using similar, but technically quite different methods, and manifestly show Belavin-Knizhnik singularities when surfaces degenerate.

We derive the g -loop, N -string amplitude (density) of the (closed) NS-string in an explicit parametrization of super moduli space for a subset of 2 g even spinstructures.

The general formalism for studying these theories is set up and some details are given concerning degenerate representations of the N=2 super Virasoro algebra in (generalized) Neveu-Schwarz and Ramond sectors. In particular the N=2 version of Kac's formula for conformal dimensions is derived.

A representation based on free fermions has been found, realizing the unitary representations of N = 2 superconformal theory when the central charge, c2, is between 0 and 1. The results confirm previous conjectures for the list of discrete values of c2 and the superconformal dimensions, h, for highest-weight states with t = 0 in the Neveu-Schwarz sector (and t = ±1 4 in the Ramond sector). Here t is the eigenvalue of the U(1) Kac-Moody current in the theory. For t ≠ 0 ( ±1 4 ) new results are obtained, including a list of possible discrete t-values and a modified list of the possible discrete h-values.

We present an approximate QCD vacuum for SU(N → ∞). It is a generalization of the ferromagnetic vacuum first obtained by Savvidy for SU(2) and generalized by one of us to SU(3) and SU(4). Problems occuring for N ⩾ 5 are handled in the large-Nlimit by a contnious formalism, and the vacuum obtained is characterized by N − 1 constant, commuting, color magnetic fields with an isotropic distribution of spatial directions. The energy density of this vacuum is lower than of the perturbative vacuum by a number proportional to N2, as expected from general large-N arguments. Like the Savvidy vacuum the large-N vacuum may decay into a variant of the domained Copenhagen vacuum. We give a lower limit on the domain size.

Nuclear Physics B232 (1984) 291-305 © North-Holland Publishing Company ON THE STATIC POTENTIAL IN POLYAKOV'S THEORY OF THE QUANTIZED STRING B. DURHUUS, P. OLESEN and J.L. PETERSEN The Niels Bohr Institute, University of Copenhagen, DK-21 O0 Copenhagen 0, Denmark Received 12 July 1983 We determine that part of the large-distance correction to the linear potential which is proportional to d, the number of spacetime dimensions. We find that the result depends in a surprising way on the parameter /, which appears in the Liouville theory that results when integrations over string fluctuations have been performed. For /* = 0 the correction is of the expected form ~'d 1 24 R' (d--+ -oe,R-+ m). However, for any/~ :~ 0 there is no 1/R potential at all with a coefficient proportional to d. 1. Introduction In this paper we study the static potential between classical "quarks" and "antiquarks" in the string model of Brink, Di Vecchia and Howe [1], following the quantization prescription of Polyakov [2] adapted to cover the case of open strings in refs. [3-5]. (For some reviews see refs. [6, 7].) Some time ago Liascher, Symanzik and Weisz [8] calculated the corresponding object in the string model of Eguchi [9]. They found in the approximation of small string fluctuations at large distances VLsw(R)=rR d-2 1 ( 1 ) - --2-a--,~ + 0 ~ , (1) where z is the string tension and d is the spacetime dimension. A similar result for the old dual string is implicit in the work of Brink and Nielsen [10] and of Minami [11]. Subsequently Alvarez [12] computed leading 1/d corrections, and Liascher [13] emphasized the generality of the result by pointing out that the coefficient of the 1/R correction of the potential is universal in the sense that it must be expected in all models where the string position is the only degree of freedom. Then the factor d - 2 is simply the number of transverse modes, the remaining 2 longitudinal modes being gauge artifacts. 291

The covariant loop calculus provides an efficient technique for computing explicit expressions for the density on moduli space corresponding to arbitrary (bosonic string) loop diagrams. Since modular invariance is not manifest, however, we carry out a detailed comparison with known explicit two- and three-loop results derived using analytic geometry (one loop is known to be okay). We establish identity to “high” order in some moduli and exactly in others. Agreement is found as a result of various non-trivial cancellations, in part related to number theory. We feel our results provide very strong support for the correctness of the covariant loop calculus approach.

An N -reggeon vertex is constructed with the inclusion of the contribution of the ghost coordinates. It is shown that it is projective and BRST invariant.

We carry out a comparison between vertices proposed by various authors by discussing the multi-loop vertices for the bosonic string and for the NS-string in terms of oscillator modes.

We present our final results for a ππ phase-shift analysis based on extrapolated moments obtained from the 17 GeV/c CERN-Munich experiment on π−p→π+π−n. Compared to our previous publication [1] the final results show no important qualitative change but the numerical accuracy is considerably improved as a result of using modified techniques both in the fixed-momentum transfer analysis and in the phase-shift analysis. As a result, various diseases of our old solution have been cured. We analyze in some detail the coupling of the ϱ′(1600) to 2π, clearly seen in our solution. We argue that our technique has solved the phase-shift ambiguities previously obtained and we give details of our solution which has a very good x2 to the data as well as a high numerical consistency with fixed-t, fixed-u and fixed-s analyticity.

Field theories naturally give rise to multiple jets of hadrons in short-distance processes, such as e + e − annihilation. In particular, a low-energy jet of hadrons distributed in some cone of opening angle δ would be naively expected to evolve at high energies into multiple jets within the angle δ. We explore to what extent this will happen in quantum chromodynamics.

Reduced partial wave amplitudes for inelastic processes with two incoming and two outgoing particles are examined. Areas in the s-plane where the usual projection formula gives a non-analytic result are investigated. Continuation into these areas from inside which has been touched upon already in literature is further analysed. By redefining the continuation practical rules for doing calculations are set up and found to be formally simple. Unexpected physical peculiarities are discovered, however. Instead, a continuation from outside is found to be physically more satisfactory but formally more involved although still reasonably straightforward. Details for K N → πΣ are given.

We discuss in a general way the problem of extracting the effective KNY coupling constant from data on KN forward amplitudes. In particular we investigate the impact of the so called positivity condition recently claimed by Lopez and Yndurain to give a coupling constant determination with errors comparable to those on G 2 π NN 4π . We point out possible biases in their estimate, devise an approximation scheme related to the Pade approximation scheme free of these and perform an analysis using it. By explicit construction we show that positivity still allows a large range of coupling constants.

We perform a dispersion relation type calculation of the I = 0 S-wave amplitude g0+ (t) for the process ππ → K K , in the region from t = 4μ2 to t = (1100 MeV)2. Crossing is imposed by generalizing the newly developed hyperbolic partial-wave relations to our reaction and by imposing them on our amplitude using experimental Kπ phase-shift information as input. Analyticity and unitarity is imposed by generalizing the formalism of BFP [1] for parametrizing partial-wave amplitudes. This readily allows us to impose the experimental ππ → K K cross section. Finally the low energy behaviour is constrained to lie within certain limits recently deduced from fixed-tKπ dispersion relation studies [2] and including the current algebra prediction as a special case. We are able to resolve a previous controversy regarding the sign of Im g0(+) (t).

We construct a supersymmetric version of the Wess-Zumino action in two dimensions. For a special value of the coupling constant γ 2 = 4 π / n it turns out that this theory consists of the original WZ action plus free fermions in the adjoint representation. By bosonization such a theory should be equivalent to a theory of two sets of free fermions. We study in some detail how supersymmetry is realized in these two theories. We further develop the general formalism for studying any two-dimensional quantum theory that is superconformal and super-Kac-Moody invariant, the SWZ theory and the particular free Fermi theory being examples. We generalize and apply this formalism to prove the equivalence of SWZ to a free Fermi theory.

We derive properties of unitary highest weight representations of the N = 4 superconformal algebras in 2 dimensions, characterized by two SU(2)Kac-Moody subalgebras. For the range 3 ⩽ c < 6 we can prove that we have constructed all unitary highest weight representations. These reduce in N = 2 to the discrete series. For other values of the parameters we derive bounds on the values of h, and we conjecture that these are complete. This is motivated by explicit constructions of representations for various values of the parameters. For the so-called massless representations we do indeed prove that our treatment is complete.

A general method for obtaining ratios of coupling constants (defined by pole residues) in a way which is completely free of resonance /background separation troubles is devised and applied to the epsilon -meson. Huge discrepancies between previous determinations are shown to arise (i) from inherent ambiguities in the methods used, (ii) from lack of knowledge about the epsilon -pole position and (iii) from the well-known up-down ambiguity in the isospin-0 s-wave pi pi phase shift delta /sub 0//sup o/. Taking as input pi N phase shifts, available information on delta /sup 0//sub 0/ and including all possible uncertainties, the authors find for down-up or up-up delta /sup 0//sub 0/: g/sub epsilon NN//g/sub epsilon pi pi /=(6+or-3) mu /sup -1/, and for down-down or up-up delta /sup 0//sub 0/: g/sub epsilon NN//g/sub epsilon pi pi /=(1.8+or-0.5) mu /sup -1/ The precise validity of the scale invariance breaking prediction (g/sub epsilon NN//g/sub epsilon pi pi /). m/sup 2//sub epsilon //2M=1 is fulfilled in some theoretical pi pi models having Gamma /sub epsilon / approximately=m/sub epsilon / approximately=500 MeV and delta /sup 0//sub 0/ of up-down type, but is excluded if sigma /sup 0//sub 0/ is down-up or up-up. (15 refs).