A quantitative approach for measuring the reservoir of latent HIV-1 proviruses.

A stable latent reservoir for HIV-1 in resting CD4+ T cells is the principal barrier to a cure1-3. Curative strategies that target the reservoir are being tested4,5 and require accurate, scalable reservoir assays. The reservoir was defined with quantitative viral outgrowth assays for cells that release infectious virus after one round of T cell activation1. However, these quantitative outgrowth assays and newer assays for cells that produce viral RNA after activation6 may underestimate the reservoir size because one round of activation does not induce all proviruses7. Many studies rely on simple assays based on polymerase chain reaction to detect proviral DNA regardless of transcriptional status, but the clinical relevance of these assays is unclear, as the vast majority of proviruses are defective7-9. Here we describe a more accurate method of measuring the HIV-1 reservoir that separately quantifies intact and defective proviruses. We show that the dynamics of cells that carry intact and defective proviruses are different in vitro and in vivo. These findings have implications for targeting the intact proviruses that are a barrier to curing HIV infection

Roles of the Amino Terminal Region and Repeat Region of the Plasmodium berghei Circumsporozoite Protein in Parasite Infectivity

The circumsporozoite protein (CSP) plays a key role in malaria sporozoite infection of both mosquito salivary glands and the vertebrate host. The conserved Regions I and II have been well studied but little is known about the immunogenic central repeat region and the N-terminal region of the protein. Rodent malaria Plasmodium berghei parasites, in which the endogenous CS gene has been replaced with the avian Plasmodium gallinaceum CS (PgCS) sequence, develop normally in the A. stephensi mosquito midgut but the sporozoites are not infectious. We therefore generated P. berghei transgenic parasites carrying the PgCS gene, in which the repeat region was replaced with the homologous region of P. berghei CS (PbCS). A further line, in which both the N-terminal region and repeat region were replaced with the homologous regions of PbCS, was also generated. Introduction of the PbCS repeat region alone, into the PgCS gene, did not rescue sporozoite species-specific infectivity. However, the introduction of both the PbCS repeat region and the N-terminal region into the PgCS gene completely rescued infectivity, in both the mosquito vector and the mammalian host. Immunofluorescence experiments and western blot analysis revealed correct localization and proteolytic processing of CSP in the chimeric parasites. The results demonstrate, in vivo, that the repeat region of P. berghei CSP, alone, is unable to mediate sporozoite infectivity in either the mosquito or the mammalian host, but suggest an important role for the N-terminal region in sporozoite host cell invasion

The small angle tile calorimeter in the DELPHI experiment

The {\bf S}mall angle {\bf TI}le {\bf C}alorimeter ({\bf STIC}) provides calorimetric coverage in the very forward region of the DELPHI experiment at the CERN LEP collider. The structure of the calorimeters, built with a so-called ``shashlik'' technique, gives a perfectly hermetic calorimeter and still allows for the insertion of tracking detectors within the sampling structure to measure the direction of the showering particle. A charged-particle veto system, composed of two scintillator layers, makes it possible to trigger on single photon events and provides e-$\gamma$ separat ion. Results are presented from the extensive studies of these detectors in the CERN testbeams prior to installation and of the detector performance at LEP

Search for Neutral Heavy Leptons Produced in Z Decays

Weak isosinglet Neutral Heavy Leptons ($\nu_m$) have been searched for using data collected by the DELPHI detector corresponding to $3.3\times 10^{6}$ hadronic~Z$^{0}$ decays at LEP1. Four separate searches have been performed, for short-lived $\nu_m$ production giving monojet or acollinear jet topologies, and for long-lived $\nu_m$ giving detectable secondary vertices or calorimeter clusters. No indication of the existence of these particles has been found, leading to an upper limit for the branching ratio $BR($Z$^0\rightarrow \nu_m \overline{\nu})$ of about $1.3\times10^{-6}$ at 95\% confidence level for $\nu_m$ masses between 3.5 and 50 GeV/$c^2$. Outside this range the limit weakens rapidly with the $\nu_m$ mass. %Special emphasis has been given to the search for monojet--like topologies. One event %has passed the selection, in agreement with the expectation from the reaction: %$e^+e^- \rightarrow\ell \bar\ell \nu\bar\nu$. The results are also interpreted in terms of limits for the single production of excited neutrinos

Measurement of inclusive π0\pi^{0} production in hadronic Z0Z^{0} decays

An analysis is presented of inclusive \pi^0 production in Z^0 decays measured with the DELPHI detector. At low energies, \pi^0 decays are reconstructed by \linebreak using pairs of converted photons and combinations of converted photons and photons reconstructed in the barrel electromagnetic calorimeter (HPC). At high energies (up to x_p = 2 \cdot p_{\pi}/\sqrt{s} = 0.75) the excellent granularity of the HPC is exploited to search for two-photon substructures in single showers. The inclusive differential cross section is measured as a function of energy for {q\overline q} and {b \bar b} events. The number of \pi^0's per hadronic Z^0 event is N(\pi^0)/ Z_{had}^0 = 9.2 \pm 0.2 \mbox{(stat)} \pm 1.0 \mbox{(syst)} and for {b \bar b}~events the number of \pi^0's is {\mathrm N(\pi^0)/ b \overline b} = 10.1 \pm 0.4 \mbox{(stat)} \pm 1.1 \mbox{(syst)} . The ratio of the number of \pi^0's in b \overline b events to hadronic Z^0 events is less affected by the systematic errors and is found to be 1.09 \pm 0.05 \pm 0.01. The measured \pi^0 cross sections are compared with the predictions of different parton shower models. For hadronic events, the peak position in the \mathrm \xi_p = \ln(1/x_p) distribution is \xi_p^{\star} = 3.90^{+0.24}_{-0.14}. The average number of \pi^0's from the decay of primary \mathrm B hadrons is found to be {\mathrm N} (B \rightarrow \pi^0 \, X)/\mbox{B hadron} = 2.78 \pm 0.15 \mbox{(stat)} \pm 0.60 \mbox{(syst)}

Search for new phenomena using single photon events in the DELPHI detector at LEP

Data are presented on the reaction \epem~\into~\gamma + no other detected particle at center-of-mass energies, \sqs = 89.48 GeV, 91.26 GeV and 93.08 GeV. The cross section for this reaction is related directly to the number of light neutrino generations which couple to the \zz boson, and to several other phenomena such as excited neutrinos, the production of an invisible `X' particle, a possible magnetic moment of the tau neutrino, and neutral monojets. Based on the observed number of single photon events, the number of light neutrinos which couple to the \zz is measured to be N_\nu = 3.15 \pm 0.34. No evidence is found for anomalous production of energetic single photons, and upper limits at the 95\% confidence level are determined for excited neutrino production (BR < 4-9 \times 10^{-6}), production of an invisible `X' particle (\sigma < 0.1 pb), and the magnetic moment of the tau neutrino (< 5.2 \times 10^{-6} \mu_B). No event with the topology of a neutral monojet is found, and this corresponds to the limit \sigma < 0.044/\epsilon pb at the 95\% confidence level, where \epsilon is the unknown overall monojet detection efficiency

Measurement of the Bd0^{0}_{d} oscillation frequency using kaons, leptons and jet charge

A measurement of the mass difference, \Delta m_d, between the two physical \mbox{B}^0_d states has been obtained from the analysis of the impact parameter distribution of a lepton emitted at large transverse momentum (p_t) relative to the jet axis and from the analysis of the flight distance distribution of secondary vertices tagged by either a high p_t lepton or an identified kaon. In the opposite hemisphere of the event, the charge of the initial quark has been evaluated using a high p_t lepton, a charged kaon or the mean jet charge. With 1.7 million hadronic Z^0 decays recorded by DELPHI between 1991 and 1993, \Delta m_d is found to be: \Delta m_d = 0.531^{+0.050}_{-0.046} ~(stat.) \pm 0.078 ~(syst.) ~ {\mathrm{ps}}^{-1} \,

Energy dependence of the differences between the quark and gluon jet fragmentation

Three jet events arising from decays of the Z boson, collected by the DELPHI detector, were used to measure differences in quark and gluon fragmentation. Gluon jets were anti-tagged by identifying b quark jets. Unbiased quark jets came from events with two jets plus one photon. Quark and gluon jet properties in different energy ranges were compared for the first time within the same detector. Quark and gluon jets of nearly the same energy in symmetric three jet event topologies were also compared. Using three independent methods, the average value of the ratio of the mean charged multiplicities of gluon and quark jets is $$=1.241\pm 0.015\ (stat.) \pm 0.025\ (syst.).$$ Gluon jets are broader and produce fragments with a softer energy spectrum than quark jets of equivalent energy. The string effect has been observed in fully symmetric three jet events. The measured ratio R_{\gamma} of the charged particle flow in the q\overline{q} inter-jet region of the q\bar{q}g and q\bar{q}\gamma samples agrees with the perturbative QCD expectation. The dependence of the mean charged multiplicity on the hadronic center-of-mass energy was analysed in photon plus n-jet events. The value for \alpha_s(M_Z) determined from these data using a QCD prediction with corrections at leading and next-to-leading order is \[ \alpha_s(M_Z)=0.116 \pm 0.003\ (stat.) \pm 0.009\ (syst.). \