Normal, dust-obscured galaxies in the epoch of reionization.

Over the past decades, rest-frame ultraviolet (UV) observations have provided large samples of UV luminous galaxies at redshift (z) greater than 6 (refs. 1-3), during the so-called epoch of reionization. While a few of these UV-identified galaxies revealed substantial dust reservoirs4-7, very heavily dust-obscured sources at these early times have remained elusive. They are limited to a rare population of extreme starburst galaxies8-12 and companions of rare quasars13,14. These studies conclude that the contribution of dust-obscured galaxies to the cosmic star formation rate density at z > 6 is sub-dominant. Recent ALMA and Spitzer observations have identified a more abundant, less extreme population of obscured galaxies at z = 3-6 (refs. 15,16). However, this population has not been confirmed in the reionization epoch so far. Here, we report the discovery of two dust-obscured star-forming galaxies at z = 6.6813 ± 0.0005 and z = 7.3521 ± 0.0005. These objects are not detected in existing rest-frame UV data and were discovered only through their far-infrared [C II] lines and dust continuum emission as companions to typical UV-luminous galaxies at the same redshift. The two galaxies exhibit lower infrared luminosities and star-formation rates than extreme starbursts, in line with typical star-forming galaxies at z ≈ 7. This population of heavily dust-obscured galaxies appears to contribute 10-25% to the z > 6 cosmic star formation rate density.

Multi-element logic gates for trapped-ion qubits.

Precision control over hybrid physical systems at the quantum level is important for the realization of many quantum-based technologies. In the field of quantum information processing (QIP) and quantum networking, various proposals discuss the possibility of hybrid architectures where specific tasks are delegated to the most suitable subsystem. For example, in quantum networks, it may be advantageous to transfer information from a subsystem that has good memory properties to another subsystem that is more efficient at transporting information between nodes in the network. For trapped ions, a hybrid system formed of different species introduces extra degrees of freedom that can be exploited to expand and refine the control of the system. Ions of different elements have previously been used in QIP experiments for sympathetic cooling, creation of entanglement through dissipation, and quantum non-demolition measurement of one species with another. Here we demonstrate an entangling quantum gate between ions of different elements which can serve as an important building block of QIP, quantum networking, precision spectroscopy, metrology, and quantum simulation. A geometric phase gate between a (9)Be(+) ion and a (25)Mg(+) ion is realized through an effective spin-spin interaction generated by state-dependent forces induced with laser beams. Combined with single-qubit gates and same-species entangling gates, this mixed-element entangling gate provides a complete set of gates over such a hybrid system for universal QIP. Using a sequence of such gates, we demonstrate a CNOT (controlled-NOT) gate and a SWAP gate. We further demonstrate the robustness of these gates against thermal excitation and show improved detection in quantum logic spectroscopy. We also observe a strong violation of a CHSH (Clauser-Horne-Shimony-Holt)-type Bell inequality on entangled states composed of different ion species.

Dissipative production of a maximally entangled steady state of two quantum bits.

Entangled states are a key resource in fundamental quantum physics, quantum cryptography and quantum computation. Introduction of controlled unitary processes--quantum gates--to a quantum system has so far been the most widely used method to create entanglement deterministically. These processes require high-fidelity state preparation and minimization of the decoherence that inevitably arises from coupling between the system and the environment, and imperfect control of the system parameters. Here we combine unitary processes with engineered dissipation to deterministically produce and stabilize an approximate Bell state of two trapped-ion quantum bits (qubits), independent of their initial states. Compared with previous studies that involved dissipative entanglement of atomic ensembles or the application of sequences of multiple time-dependent gates to trapped ions, we implement our combined process using trapped-ion qubits in a continuous time-independent fashion (analogous to optical pumping of atomic states). By continuously driving the system towards the steady state, entanglement is stabilized even in the presence of experimental noise and decoherence. Our demonstration of an entangled steady state of two qubits represents a step towards dissipative state engineering, dissipative quantum computation and dissipative phase transitions. Following this approach, engineered coupling to the environment may be applied to a broad range of experimental systems to achieve desired quantum dynamics or steady states. Indeed, concurrently with this work, an entangled steady state of two superconducting qubits was demonstrated using dissipation.

High-Fidelity Universal Gate Set for

We report high-fidelity laser-beam-induced quantum logic gates on magnetic-field-insensitive qubits comprised of hyperfine states in ^{9}Be^{+} ions with a memory coherence time of more than 1 s. We demonstrate single-qubit gates with an error per gate of 3.8(1)×10^{-5}. By creating a Bell state with a deterministic two-qubit gate, we deduce a gate error of 8(4)×10^{-4}. We characterize the errors in our implementation and discuss methods to further reduce imperfections towards values that are compatible with fault-tolerant processing at realistic overhead.

Preparation of Entangled States through Hilbert Space Engineering.

We apply laser fields to trapped atomic ions to constrain the quantum dynamics from a simultaneously applied global microwave field to an initial product state and a target entangled state. This approach comes under what has become known in the literature as "quantum Zeno dynamics" and we use it to prepare entangled states of two and three ions. With two trapped ^{9}Be^{+} ions, we obtain Bell state fidelities up to 0.990_{-5}^{+2}; with three ions, a W-state fidelity of 0.910_{-7}^{+4} is obtained. Compared to other methods of producing entanglement in trapped ions, this procedure can be relatively insensitive to certain imperfections such as fluctuations in laser intensity.

Sympathetic electromagnetically-induced-transparency laser cooling of motional modes in an ion chain.

We use electromagnetically-induced-transparency laser cooling to cool motional modes of a linear ion chain. As a demonstration, we apply electromagnetically-induced-transparency cooling on 24Mg+ ions to cool the axial modes of a 9Be+-24Mg+ ion pair and a 9Be+-24Mg+-24Mg+-9Be+ ion chain, thereby sympathetically cooling the 9Be+ ions. Compared to previous implementations of conventional Raman sideband cooling, we achieve approximately an order-of-magnitude reduction in the duration required to cool the modes to near the ground state and significant reduction in required laser intensity.

Demonstration of a dressed-state phase gate for trapped ions.

We demonstrate a trapped-ion entangling-gate scheme proposed by Bermudez et al. [Phys. Rev. A 85, 040302 (2012)]. Simultaneous excitation of a strong carrier and a single-sideband transition enables deterministic creation of entangled states. The method works for magnetic field-insensitive states, is robust against thermal excitations, includes dynamical decoupling from qubit dephasing errors, and provides simplifications in experimental implementation compared to some other entangling gates with trapped ions. We achieve a Bell state fidelity of 0.974(4) and identify the main sources of error.

Coherent diabatic ion transport and separation in a multizone trap array.

We investigate the dynamics of single and multiple ions during transport between and separation into spatially distinct locations in a multizone linear Paul trap. A single 9Be+ ion in a ~2 MHz harmonic well was transported 370 µm in 8 µs, corresponding to 16 periods of oscillation, with a gain of 0.1 motional quanta. Similar results were achieved for the transport of two ions. We also separated chains of up to 9 ions from one potential well to two distinct potential wells. With two ions this was accomplished in 55 µs, with excitations of approximately two quanta for each ion. Fast transport and separation can significantly reduce the time overhead in certain architectures for scalable quantum information processing with trapped ions.

Randomized benchmarking of multiqubit gates.

We describe an extension of single-qubit gate randomized benchmarking that measures the error of multiqubit gates in a quantum information processor. This platform-independent protocol evaluates the performance of Clifford unitaries, which form a basis of fault-tolerant quantum computing. We implemented the benchmarking protocol with trapped ions and found an error per random two-qubit Clifford unitary of 0.162±0.008, thus setting the first benchmark for such unitaries. By implementing a second set of sequences with an extra two-qubit phase gate inserted after each step, we extracted an error per phase gate of 0.069±0.017. We conducted these experiments with transported, sympathetically cooled ions in a multizone Paul trap-a system that can in principle be scaled to larger numbers of ions.

Unique and shared systemic biomarkers for emphysema in Alpha-1 Antitrypsin deficiency and chronic obstructive pulmonary disease.

BACKGROUND: Alpha-1 Antitrypsin (AAT) deficiency (AATD), the most common genetic cause of emphysema presents with unexplained phenotypic heterogeneity in affected subjects. Our objectives to identify unique and shared AATD plasma biomarkers with chronic obstructive pulmonary disease (COPD) may explain AATD phenotypic heterogeneity. METHODS: The plasma or serum of 5,924 subjects from four AATD and COPD cohorts were analyzed on SomaScan V4.0 platform. Using multivariable linear regression, inverse variance random-effects meta-analysis, and Least Absolute Shrinkage and Selection Operator (LASSO) regression we tested the association between 4,720 individual proteins or combined in a protein score with emphysema measured by 15th percentile lung density (PD15) or diffusion capacity (DLCO) in distinct AATD genotypes (Pi*ZZ, Pi*SZ, Pi*MZ) and non-AATD, PiMM COPD subjects. AAT SOMAmer accuracy for identifying AATD was tested using receiver operating characteristic curve analysis. FINDINGS: In PiZZ AATD subjects, 2 unique proteins were associated with PD15 and 98 proteins with DLCO. Of those, 68 were also associated with DLCO in COPD also and enriched for three cellular component pathways: insulin-like growth factor, lipid droplet, and myosin complex. PiMZ AATD subjects shared similar proteins associated with DLCO as COPD subjects. Our emphysema protein score included 262 SOMAmers and predicted emphysema in AATD and COPD subjects. SOMAmer AAT level <7.99 relative fluorescence unit (RFU) had 100% sensitivity and specificity for identifying Pi*ZZ, but it was lower for other AATD genotypes. INTERPRETATION: Using SomaScan, we identified unique and shared plasma biomarkers between AATD and COPD subjects and generated a protein score that strongly associates with emphysema in COPD and AATD. Furthermore, we discovered unique biomarkers associated with DLCO and emphysema in PiZZ AATD. FUNDING: This work was supported by a grant from the Alpha-1 Foundation to RPB. COPDGene was supported by Award U01 HL089897 and U01 HL089856 from the National Heart, Lung, and Blood Institute. Proteomics for COPDGene was supported by NIH 1R01HL137995. GRADS was supported by Award U01HL112707, U01 HL112695 from the National Heart, Lung, and Blood Institute, and UL1TRR002535 to CCTSI; QUANTUM-1 was supported by the National Heart Lung and Blood Institute, the Office of Rare Diseases through the Rare Lung Disease Clinical Research Network (1 U54 RR019498-01, Trapnell PI), and the Alpha-1 Foundation. COPDGene is also supported by the COPD Foundation through contributions made to an Industry Advisory Board that has included AstraZeneca, Bayer Pharmaceuticals, Boehringer-Ingelheim, Genentech, GlaxoSmithKline, Novartis, Pfizer, and Sunovion.

SELDI-TOF derived serum biomarkers failed to differentiate between patients with beryllium sensitisation and patients with chronic beryllium disease.

BACKGROUND: People exposed to beryllium may develop beryllium sensitisation (BeS) and, in some cases, progress to chronic beryllium disease (CBD). OBJECTIVES: The objective of this study was to test the ability of proteomic technology to identify patterns of serum protein biomarkers that allow differentiation between BeS and CBD and thus remove the need for invasive bronchoscopic procedures. METHODS: Initially, SELDI-TOF methodology and analysis was performed on serum samples from 30 CBD and 31 BeS patients. RESULTS: This 'starter set' yielded two distinct biomarker pattern sets with eight candidate proteins. The first set differentiated between BeS and CBD with 83.3% sensitivity and 82.3% specificity, with 10-fold cross-validation of 75% and 79%, respectively. The second set of biomarkers yielded higher sensitivity (90.0%) and higher specificity (90.3%), with 10-fold cross-validation of 71.7% and 82.3%, respectively. Due to its greater sensitivity and specificity, the second set of biomarkers was used as the framework for differentiating between CBD and BeS in a second set of serum samples from 450 patients with BeS and CBD. When this larger set of samples was subjected to the biomarker framework in a blinded fashion, it yielded a sensitivity of 43.53% and a specificity of 38.93%. CONCLUSIONS: Due to these low sensitivity and specificity values, we have concluded that, currently, the unique set of SELDI-TOF derived biomarkers does not possess the qualities that would allow it to differentiate between a CBD patient and a BeS patient using serum protein biomarkers. Future refinements in sample collection or proteomic technology may be needed to improve biomarker discovery.

Polymorphisms in the superoxide dismutase-3 gene are associated with emphysema in COPD.

Superoxide dismutase-3 (SOD3) is a major extracellular antioxidant enzyme, and previous studies have indicated a possible role of this gene in chronic obstructive pulmonary disease (COPD). We hypothesized that polymorphisms in the SOD3 gene would be associated with COPD and COPD-related phenotypes. We genotyped three SOD3 polymorphisms (rs8192287 (E1), rs8192288 (I1), and rs1799895 (R213G)) in a case-control cohort, with severe COPD cases from the National Emphysema Treatment Trial (NETT, n = 389) and smoking controls from the Normative Aging Study (NAS, n = 472). We examined whether the single nucleotide polymorphisms (SNPs) were associated with COPD status, lung function variables, and quantitative computed tomography (CT) measurements of emphysema and airway wall thickness. Furthermore, we tried to replicate our initial findings in two family-based studies, the International COPD Genetics Network (ICGN, n = 3061) and the Boston Early-Onset COPD Study (EOCOPD, n = 949). In NETT COPD cases, the minor alleles of SNPs E1 and I1 were associated with a higher percentage of emphysema (%LAA950) on chest CT scan (p = .029 and p = .0058). The association with E1 was replicated in the ICGN family study, where the minor allele was associated with more emphysema (p = .048). Airway wall thickness was positively associated with the E1 SNP in ICGN; however, this finding was not confirmed in NETT. Quantitative CT data were not available in EOCOPD. The SNPs were not associated with lung function variables or COPD status in any of the populations. In conclusion, polymorphisms in the SOD3 gene were associated with CT emphysema but not COPD susceptibility, highlighting the importance of phenotype definition in COPD genetics studies.

Tumour necrosis factor gene polymorphisms are associated with COPD.

Tumour necrosis factor (TNF)-alpha has been shown to be an important factor in animal models of chronic obstructive pulmonary disease (COPD). However, human studies of TNF polymorphisms in COPD have been equivocal. Six TNF single nucleotide polymorphisms (-1031C/T, -863C/A, -857C/T, -237G/A, -308G/A and +487G/A) and their haplotypes were investigated in 423 Caucasian smokers (298 patients with spirometric evidence of COPD and 125 without airflow obstruction). The -308 minor allele (A) had a higher odds ratio (OR) of being associated with COPD in multivariate analysis (controlling for age, sex, pack-yrs; OR 1.9, 95% confidence interval (CI) 1.1-3.2) and was also associated with worse forced expiratory volume in one second/forced vital capacity. The -237 minor allele (A) had a lower OR of being associated with COPD (OR 0.40, 95% CI 0.19-0.86). In COPD patients, the -857 minor allele (T) had a lower OR of being associated with severe stages of COPD (Global Initiative for Obstructive Lung Disease stage III and IV versus stage I and II, OR 0.46, 95% CI 0.24-0.88). Other TNF single nucleotide polymorphisms were not associated with COPD but the -1031/-863 haplotype CC/TC had a lower OR in COPD patients versus smoking controls (OR 0.22, 95% CI 0.05-0.97). The present study adds further evidence that tumour necrosis factor genotypes play a role in susceptibility to cigarette smoke.

Environmental exposure to manganese in air: Tremor, motor and cognitive symptom profiles.

BACKGROUND: Excessive exposure to manganese (Mn) may cause parkinsonian-like motor and tremor symptoms and adverse cognitive effects, including problems with executive functioning (EF), resembling those found in later-stage Parkinson's disease (PD). Studies seeking to differentiate PD patients into subgroups with associated cognitive and functional outcomes using motor and tremor symptoms identified tremor-dominant (TD) and non-tremor dominant (NTD) subtypes. It is unclear whether differing patterns of pathophysiology and symptoms exist in Mn neurotoxicity, as they do in PD. METHODS: Residents of East Liverpool (n=83) and Marietta, OH (n=99) exposed to chronic (>10years) environmental Mn through industrial pollution were administered neuropsychological measures and a physician-rated scale of movement-disorder symptoms. Two-step cluster analysis was used to group residents based on tremor symptoms, bradykinesia/rigidity symptoms, gait disturbance, and executive function. Cluster membership was validated using modeled air-Mn exposure and a computerized tremor measure. RESULTS: Elevated tremor and motor symptoms and executive dysfunction were observed, and TD and NTD symptom clusters were identified. Two additional clusters were also identified: Executive Dysfunction and Normal Functioning. The NTD residents, with elevated levels of gait disturbance and other movement disorder symptoms, did not evidence EF impairment, as predicted. Instead, residents with EF impairment formed their own cluster, and were relatively free of movement disorder symptoms. CONCLUSIONS: Results resemble reports in the PD literature with TD and NTD clusters identified, but executive dysfunction did not cluster with NTD symptoms. PD and Mn exposure likely have differing pathophysiology and developmental courses, and therefore different symptom patterns, even when similar symptoms are present.

Association of MRI T1 relaxation time with neuropsychological test performance in manganese- exposed welders.

This study examines the results of neuropsychological testing of 26 active welders and 17 similar controls and their relationship to welders' shortened MRI T1 relaxation time, indicative of increased brain manganese (Mn) accumulation. Welders were exposed to Mn for an average duration of 12.25 years to average levels of Mn in air of 0.11±0.05mg/m3. Welders scored significantly worse than controls on Fruit Naming and the Parallel Lines test of graphomotor tremor. Welders had shorter MRI T1 relaxation times than controls in the globus pallidus, substantia nigra, caudate nucleus, and the anterior prefrontal lobe. 63% of the variation in MRI T1 relaxation times was accounted for by exposure group. In welders, lower relaxation times in the caudate nucleus and substantia nigra were associated with lower neuropsychological test performance on tests of verbal fluency (Fruit Naming), verbal learning, memory, and perseveration (WHO-UCLA AVLT). Results indicate that verbal function may be one of the first cognitive domains affected by brain Mn deposition in welders as reflected by MRI T1 relaxation times.

Prolongation of the P-300 latency associated with hydrogen sulfide exposure.

Three patients exposed to hydrogen sulfide developed persistent cognitive impairment, as suggested by the P-300 event-related potential and measured by neuropsychological testing. Routine neurological and physical examinations were unremarkable, although the patients were sufficiently impaired so as to be unable to work. The P-300 event-related potential and neuropsychological testing proved to be important in the detection of cognitive dysfunction following acute hydrogen sulfide exposure. The three patients with neurocognitive dysfunction were acutely exposed to hydrogen sulfide. The incidents occurred independently and under different circumstances. Each patient was evaluated at the Northern California Occupational Health Clinic, San Francisco, examined neurologically and neuropsychologically, and evaluated with a P-300 event-related potential. Each patient had persistent neurological symptoms, neuropsychological deficit, and abnormally prolonged P-300 latencies.

Massive hemoptysis from a pulmonary artery aneurysm associated with an emphysematous bulla.

A 66-year-old man with a history of COPD and Aspergillus fumigatus infection developed massive hemoptysis. Pulmonary artery angiography revealed an aneurysm which was successfully treated with coil embolization. This is the first known report of a pulmonary artery aneurysm causing massive hemoptysis in a patient with bullous emphysema.

Persistent respiratory health effects after a metam sodium pesticide spill.

STUDY OBJECTIVE: To report the occurrence of persistent respiratory disorders, including irritant-induced asthma, among adults living and working near an environmental spill of the pesticide, metam sodium, after the derailment of a tank car. DESIGN: Retrospective clinical case series. SETTING: California communities situated within one-half mile of the Sacramento River, from Mt. Shasta City to Shasta Lake. PATIENTS: 197 adults referred to a university occupational/environmental health clinic or to a private occupational/environmental health practitioner for evaluation of health problems potentially related to the spill. MEASUREMENTS AND RESULTS: History, physical examination, review of medical records, spirometry, and methacholine challenge testing revealed 20 cases of persistent irritant-induced asthma and 10 cases of persistent exacerbation of asthma. CONCLUSIONS: This is the first reported series of cases of persistent irritant-induced asthma involving both community residents and occupationally exposed individuals.

Isolated pulmonary capillaritis and diffuse alveolar hemorrhage in rheumatoid arthritis and mixed connective tissue disease.

STUDY OBJECTIVES: To demonstrate that pulmonary capillaritis and diffuse alveolar hemorrhage (DAH) occur and are isolated to the lung and therefore not part of systemic vasculitis at the time of the DAH episode in rheumatoid arthritis (RA) and mixed connective tissue disease (MCTD). DESIGN: Lung biopsy specimens from patients with DAH were reviewed and those with the histologic features of pulmonary capillaritis were identified. SETTING: The patients were selected from seven Denver-area general hospitals. PATIENTS: Fifty-eight patients with biopsy specimen proved pulmonary capillaritis (1991 to 1997) were identified and classified according to disease. Three patients met the American Rheumatism Association criteria for RA and one patient fulfilled clinical and serologic criteria for MCTD. INTERVENTIONS: All clinical, laboratory, and radiographic data on initial presentation and at follow-up periods were extracted from the charts of the four study patients. Histologic slides were reviewed and immunofluorescent studies of lung tissue were performed. MEASUREMENTS AND RESULTS: All four patients had a connective tissue disease diagnosis prior to the DAH episode. Symptoms referable to pulmonary capillaritis were of short duration (2 to 14 days) and there was no clinical or serologic evidence for an accompanying systemic vasculitis, in particular glomeronephritis. Three patients, two with RA and one with MCTD, demonstrated pulmonary immune complex deposition. Three resolved their illness following IV methylprednisilone and cyclophosphamide therapy. One RA patient died following a myocardial infarction. In the three survivors, no further episodes of DAH have occurred after a mean of 24 months (range, 10 to 48 months). CONCLUSIONS: To our knowledge, these are the first cases of DAH due to pulmonary capillaritis documented to complicate RA and MCTD. The capillaritis was not part of a systemic vasculitis at the time of the DAH episode, but rather represented an isolated small-vessel vasculitis of the lungs in this group of patients. Immune complex deposition may be involved in the pathogenesis.

Extracellular superoxide dismutase overexpression improves behavioral outcome from closed head injury in the mouse.

Oxidative stress is known to play an important role in the response of brain to traumatic insults. We tested the hypothesis that increased extracellular superoxide dismutase (EC-SOD) expression can reduce injury in a mouse model of closed head injury. Neurologic, cognitive, and histologic outcomes were compared between transgenic mice exhibiting a fivefold increase in EC-SOD activity and wild-type littermate controls. Severe or moderate transcranial impact was induced in anesthetized and physiologically controlled animals. After severe impact, transgenic mice had better neurological outcome at 24 hr postinjury (p = 0.038). Brain water content was increased, but there was no difference between groups. Moderate impact resulted in predominantly mild neurologic deficits in both groups at both 24 hr and 14 days postinjury. Morris water maze performance, testing cognitive function at 14-17 days after trauma, was better in EC-SOD overexpressors (p = 0.018). No differences were observed between groups for histologic damage in hippocampal CA1 and CA3. We conclude that EC-SOD has a beneficial effect on behavioral outcome after both severe and moderate closed head injury in mice. Because EC-SOD is believed to be predominantly located in the extracellular space, these data implicate an adverse effect of extracellular superoxide anion on outcome from closed head injury.