A quantum enhanced search for dark matter axions.

The manipulation of quantum states of light1 holds the potential to enhance searches for fundamental physics. Only recently has the maturation of quantum squeezing technology coincided with the emergence of fundamental physics searches that are limited by quantum uncertainty2,3. In particular, the quantum chromodynamics axion provides a possible solution to two of the greatest outstanding problems in fundamental physics: the strong-CP (charge-parity) problem of quantum chromodynamics4 and the unknown nature of dark matter5-7. In dark matter axion searches, quantum uncertainty manifests as a fundamental noise source, limiting the measurement of the quadrature observables used for detection. Few dark matter searches have approached this limit3,8, and until now none has exceeded it. Here we use vacuum squeezing to circumvent the quantum limit in a search for dark matter. By preparing a microwave-frequency electromagnetic field in a squeezed state and near-noiselessly reading out only the squeezed quadrature9, we double the search rate for axions over a mass range favoured by some recent theoretical projections10,11. We find no evidence of dark matter within the axion rest energy windows of 16.96-17.12 and 17.14-17.28 microelectronvolts. Breaking through the quantum limit invites an era of fundamental physics searches in which noise reduction techniques yield unbounded benefit compared with the diminishing returns of approaching the quantum limit.

Determining g_{A}/g_{V} with High-Resolution Spectral Measurements Using a LiInSe_{2} Bolometer.

Neutrinoless double beta decay (0νßß) processes sample a wide range of intermediate forbidden nuclear transitions, which may be impacted by quenching of the axial vector coupling constant (g_{A}/g_{V}), the uncertainty of which plays a pivotal role in determining the sensitivity reach of 0νßß experiments. In this Letter, we present measurements performed on a high-resolution LiInSe_{2} bolometer in a "source=detector" configuration to measure the spectral shape of the fourfold forbidden ß decay of ^{115}In. The value of g_{A}/g_{V} is determined by comparing the spectral shape of theoretical predictions to the experimental ß spectrum taking into account various simulated background components as well as a variety of detector effects. We find evidence of quenching of g_{A}/g_{V} at >5σ with a model-dependent quenching factor of 0.655±0.002 as compared to the free-nucleon value for the interacting shell model. We also measured the ^{115}In half-life to be [5.18±0.06(stat)_{-0.015}^{+0.005}(sys)]×10^{14} yr within the interacting shell model framework. This Letter demonstrates the power of the bolometeric technique to perform precision nuclear physics single-ß decay measurements, which along with improved nuclear modeling can help reduce the uncertainties in the calculation of several decay nuclear matrix elements including those used in 0νßß sensitivity calculations.

New Limit for Neutrinoless Double-Beta Decay of

The CUPID-Mo experiment at the Laboratoire Souterrain de Modane (France) is a demonstrator for CUPID, the next-generation ton-scale bolometric 0νßß experiment. It consists of a 4.2 kg array of 20 enriched Li_{2}^{100}MoO_{4} scintillating bolometers to search for the lepton-number-violating process of 0νßß decay in ^{100}Mo. With more than one year of operation (^{100}Mo exposure of 1.17 kg×yr for physics data), no event in the region of interest and, hence, no evidence for 0νßß is observed. We report a new limit on the half-life of 0νßß decay in ^{100}Mo of T_{1/2}>1.5×10^{24} yr at 90% C.I. The limit corresponds to an effective Majorana neutrino mass ⟨m_{ßß}⟩<(0.31-0.54) eV, dependent on the nuclear matrix element in the light Majorana neutrino exchange interpretation.

New Results from the Search for Low-Mass Weakly Interacting Massive Particles with the CDMS Low Ionization Threshold Experiment.

The CDMS low ionization threshold experiment (CDMSlite) uses cryogenic germanium detectors operated at a relatively high bias voltage to amplify the phonon signal in the search for weakly interacting massive particles (WIMPs). Results are presented from the second CDMSlite run with an exposure of 70 kg day, which reached an energy threshold for electron recoils as low as 56 eV. A fiducialization cut reduces backgrounds below those previously reported by CDMSlite. New parameter space for the WIMP-nucleon spin-independent cross section is excluded for WIMP masses between 1.6 and 5.5 GeV/c^{2}.

First direct limits on lightly ionizing particles with electric charge less than e/6.

While the standard model of particle physics does not include free particles with fractional charge, experimental searches have not ruled out their existence. We report results from the Cryogenic Dark Matter Search (CDMS II) experiment that give the first direct-detection limits for cosmogenically produced relativistic particles with electric charge lower than e/6. A search for tracks in the six stacked detectors of each of two of the CDMS II towers finds no candidates, thereby excluding new parameter space for particles with electric charges between e/6 and e/200.

Differentiation of erythroleukemic cells in the presence of inhibitors of DNA synthesis.

Erythroid differentiation can be readily induced by butyric acid in cultured erythroleukemic cells in the presence of inhibitors of DNA synthesis and in the absence of cell division. This result appears to rule out more complex models for globin gene expression which require gene replication or cell division (or both).

Mouse globin system: a functional and evolutionary analysis.

Structural and functional analysis of the mouse alpha-globin and beta-globin genes reveals that the globin genes are encoded in discontinous bits of coding information and that each gene locus is much more complex than was originally supposed. Each seems to consist of an array of several authentic genes as well as several apparently inactive pseudogenes. Comparison of the sequences of some of these genes to one another indicates that chromosomal DNA is a dynamic structure. Flanking and intervening sequences change in two ways: quickly, by duplication and extensive insertions and deletions, and slowly, by point mutation. Active coding sequences are usually limited to the slower mode of evolution. In addition to identifying fast and slow modes of evolution, it has also been possible to test the function of several signals that surround these genes and to identify those that appear to play a role in gene expression.

Antibody diversity.

Three important aspects of immunoglobulin gene organization and structure have emerged from studies of cloned immunoglobulin kappa chain genes. (i) Multiple variable genes are encoded separately in the genome of both immunoglobulin-producing and uncommitted (embryonic) cells, thereby establishing the evolutionary base for generating immunoglobulin diversity. (ii) These genes exist as many small, closely related families (subgroups) that share close sequence homology largely within their own subgroup. (iii) Comparison of two cloned variable gene segments derived from a single subgroup reveals a feature of their structure that distinguishes them from fixed genes (that is, globin genes) and provides, through extensive surrounding sequence homology, a large target for intergenic recombination. This last observation suggests that a simple recombination mechanism may account for their genetic instability in both germ line and somatic cells.

Characterization, expression, and evolution of the mouse embryonic zeta-globin gene.

We have determined the complete sequence of the embryonic alpha-like, zeta (zeta)-globin gene of the BALB/c mouse. The structure of this gene establishes the amino acid sequence of the mouse embryonic zeta-globin polypeptide chain and allows us to identify sequences within the gene that may be important for its expression. One of these is a 300-base segment that is tightly conserved between mice and humans and is located at the 5' end of the zeta-globin gene. By introducing the cloned gene into permanently transfected mouse erythroleukemic cell lines and comparing its transcript with that of zeta-globin mRNA derived from embryonic yolk sac erythrocytes, we are able to show that the cloned gene is transcriptionally active and that its transcript is correctly initiated and processed. Interestingly, the zeta-globin gene is also active when permanently transfected into an immunoglobulin-producing B-cell, a cell that presumably has tissue-specific requirements for gene expression. Further, a comparison of the amino acid coding sequence of the mouse zeta-globin gene to that of zeta-like globin genes of other species supports a revised evolutionary lineage in which goats and humans are closely related, whereas mice are further removed.

Flow sensing by pinniped whiskers.

Beside their haptic function, vibrissae of harbour seals (Phocidae) and California sea lions (Otariidae) both represent highly sensitive hydrodynamic receptor systems, although their vibrissal hair shafts differ considerably in structure. To quantify the sensory performance of both hair types, isolated single whiskers were used to measure vortex shedding frequencies produced in the wake of a cylinder immersed in a rotational flow tank. These measurements revealed that both whisker types were able to detect the vortex shedding frequency but differed considerably with respect to the signal-to-noise ratio (SNR). While the signal detected by sea lion whiskers was substantially corrupted by noise, harbour seal whiskers showed a higher SNR with largely reduced noise. However, further analysis revealed that in sea lion whiskers, each noise signal contained a dominant frequency suggested to function as a characteristic carrier signal. While in harbour seal whiskers the unique surface structure explains its high sensitivity, this more or less steady fundamental frequency might represent the mechanism underlying hydrodynamic reception in the fast swimming sea lion by being modulated in response to hydrodynamic stimuli impinging on the hair.

Genome-wide SNP analysis of Tg.AC transgenic mice reveals an oncogenic collaboration between v-Ha-ras and Ink4a, which is absent in p53 deficiency.

Oncogenesis is a progressive process often involving collaboration between various oncogenes and tumor suppressors. To identify those genes that collaborate with oncogenic ras, we took advantage of the Tg.AC transgenic mouse, a line that harbors the v-Ha-ras transgene and spontaneously develops an array of malignant tumors. By crossing Tg.AC mice on an inbred FVB background to other inbred strains, F1 mice were created that could be analysed using genome wide, single nucleotide polymorphism (SNP) screens. Loss of heterozygosity (LOH) in tumors and tumor cell lines marked a somatic event, possibly the inactivation of tumor suppressor gene(s). LOH could also represent DNA damage, a sign of genomic instability in the pretransformed cell. Nonetheless, the screens showed no evidence of such generalized genomic instability. Instead, they revealed a single region of LOH on chromosome 4 that occurred via somatic recombination/gene conversion, generating a region of isoparental disomy. This LOH provided a clue that linked v-Ha-ras to the inactivation of the Ink4a locus in 25 of 32 tumor cell lines. This collaboration is seen regardless of tumor type or genetic background. In contrast, tumors that develop in bitransgenic mice bearing both the v-Ha-ras gene and a heterozygous mutant p53 allele tend to retain the Ink4a locus and instead lose the p53 wild-type allele. This suggests that different strategies can be selected to collaborate with v-Ha-ras in tumorigenesis.

[The importance of wear couples for younger endoprosthesis patients]. / Die Bedeutung der Gleitpaarung beim jüngeren Endoprothesenpatienten.

The success and long-term survival rates of modern joint arthroplasty leads to a high patient satisfaction and, together with its technical improvements, has broadened the indications to an increasingly younger population. Limitations to the established systems are the long-term survival rates, which are mainly influenced by wear of the articulating parts and the resulting problems. Beside "classic" long-stemmed cemented shafts articulating with metal against polyethylene, short-stemmed or cup designs with a hard-hard self pairing are increasingly used in total hip arthroplasty. This paper reflects the current state of the art in joint arthroplasty for younger patients with the focus on wear couples and discusses future perspectives. Special interest is focused on the advantages and disadvantages of ceramic bearings, problems with allergies to implant components and the design of endoprostheses with regard to avoidance of impingement.

Butyric acid, a potent inducer of erythroid differentiation in cultured erythroleukemic cells.

Butyric acid is an unusually potent inducer of erythroid differentiation in cultured erythroleukemic cells. It is effective at one hundredth the concentration required of dimethylsulfoxide, a most effective inducing agent. Studies using a variety of analogues and metabolites suggest that the structural features of butyric acid are rather stringently required for induction. This effect is considered in view of the fact that butyric acid is a naturally occurring fatty acid, is effective in relatively low concentrations, and is widely used to form derivatives of cAMP.

Unusual alpha-globin-like gene that has cleanly lost both globin intervening sequences.

We have cloned and determined the nucleotide sequence of a mouse alpha-globin-like gene that entirely lacks the two intervening sequences that interrupt all globin genes thus far examined. The fact that this gene, alpha-3, is closely homologous to the normal adult alpha gene sequence suggests that it arose after the alpha/beta divergence and that it therefore must have lost its intervening sequences. The further fact that these intervening sequences have been lost cleanly--that is, in according with the G-T/A-G splicing rule of RNA--suggests, among other possibilities, that their loss may have been brought about by a gene conversion event involving the mediation of mature globin mRNA or its cDNA cognate. We propose such a mechanism that would permit the loss of either or both intervening sequences independently. Only the loss of both, however, should result in the inactivation of the globin gene, as seems to be the case with alpha-3.

An embryonically expressed gene is a target for c-Myc regulation via the c-Myc-binding sequence.

We have used a subtraction/coexpression strategy involving two different tumors derived from c-myc-bearing transgenic mice to identify a gene that is a target for c-Myc regulation. The gene, expressed in certain embryonic and adult tissues and in several (but not all) c-myc-based tumors, bears a functional c-Myc-binding sequence located 3' to its transcription start site. This sequence is required for the binding of a nuclear protein complex which, by antibody analysis, includes c-Myc. This site is also required for expression of a reporter gene in chimeric constructs transfected into c-myc-overexpressing cells and, conversely, requires c-myc cotransfection for its enhanced expression in COS cells. Furthermore, transfection of c-myc blocks the normal down-regulation of this gene, which occurs in embryonic stem cells as they undergo differentiation. This target gene encodes an anonymous cDNA (ECA39) found previously to be amplified in a teratocarcinoma cell line.

In situ hybridization reveals co-expression of embryonic and adult alpha globin genes in the earliest murine erythrocyte progenitors.

Murine erythropoiesis begins with the formation of primitive red blood cells in the blood islands of the embryonic yolk sac on day 7.5 of gestation. By analogy to human erythropoiesis, it has been thought that there is a gradual switch from the exclusive expression of the embryonic alpha-like globin (zeta) to the mature adult form (alpha) in these early mouse cells. We have used in situ hybridization to assess expression of these two globin genes during embryonic development. In contrast to what might have been expected, we find that there is simultaneous expression of both zeta and alpha genes from the very onset of erythropoiesis in the yolk sac. At no time could we detect expression of embryonic zeta globin mRNA without concomitant expression of adult alpha globin mRNA. Indeed, adult alpha transcripts exceed those of embryonic zeta in the earliest red cell precursors. Moreover, the pattern of hybridization reveals co-expression of both genes within the same cells. Even in the fetal liver, which supersedes the yolk sac as the major site of murine fetal erythropoiesis, there is a brief co-expression of zeta and alpha genes followed by the exclusive expression of the adult alpha genes. These data indicate an important difference in hematopoietic ontogeny between mouse and that of human, where zeta expression precedes that of alpha. In addition to resolving the embryonic expression of these globin genes, our results suggest that the embryonic alpha-like globin gene zeta may be physiologically redundant, even during the earliest stages of embryonic development.