Broadband, millimeter-wave antireflection coatings for large-format, cryogenic aluminum oxide optics.

We present two prescriptions for broadband ($ {\sim} 77 - 252\;{\rm GHz} $), millimeter-wave antireflection coatings for cryogenic, sintered polycrystalline aluminum oxide optics: one for large-format (700 mm diameter) planar and plano-convex elements, the other for densely packed arrays of quasi-optical elements-in our case, 5 mm diameter half-spheres (called "lenslets"). The coatings comprise three layers of commercially available, polytetrafluoroethylene-based, dielectric sheet material. The lenslet coating is molded to fit the 150 mm diameter arrays directly, while the large-diameter lenses are coated using a tiled approach. We review the fabrication processes for both prescriptions, then discuss laboratory measurements of their transmittance and reflectance. In addition, we present the inferred refractive indices and loss tangents for the coating materials and the aluminum oxide substrate. We find that at 150 GHz and 300 K the large-format coating sample achieves $ (97 \pm 2)\% $ transmittance, and the lenslet coating sample achieves $ (94 \pm 3)\% $ transmittance.

Detection of CMB-Cluster Lensing using Polarization Data from SPTpol.

We report the first detection of gravitational lensing due to galaxy clusters using only the polarization of the cosmic microwave background (CMB). The lensing signal is obtained using a new estimator that extracts the lensing dipole signature from stacked images formed by rotating the cluster-centered Stokes QU map cutouts along the direction of the locally measured background CMB polarization gradient. Using data from the SPTpol 500 deg^{2} survey at the locations of roughly 18 000 clusters with richness λ≥10 from the Dark Energy Survey (DES) Year-3 full galaxy cluster catalog, we detect lensing at 4.8σ. The mean stacked mass of the selected sample is found to be (1.43±0.40)×10^{14}M_{⊙} which is in good agreement with optical weak lensing based estimates using DES data and CMB-lensing based estimates using SPTpol temperature data. This measurement is a key first step for cluster cosmology with future low-noise CMB surveys, like CMB-S4, for which CMB polarization will be the primary channel for cluster lensing measurements.

Detection of B-mode polarization in the cosmic microwave background with data from the South Pole Telescope.

Gravitational lensing of the cosmic microwave background generates a curl pattern in the observed polarization. This "B-mode" signal provides a measure of the projected mass distribution over the entire observable Universe and also acts as a contaminant for the measurement of primordial gravity-wave signals. In this Letter we present the first detection of gravitational lensing B modes, using first-season data from the polarization-sensitive receiver on the South Pole Telescope (SPTpol). We construct a template for the lensing B-mode signal by combining E-mode polarization measured by SPTpol with estimates of the lensing potential from a Herschel-SPIRE map of the cosmic infrared background. We compare this template to the B modes measured directly by SPTpol, finding a nonzero correlation at 7.7σ significance. The correlation has an amplitude and scale dependence consistent with theoretical expectations, is robust with respect to analysis choices, and constitutes the first measurement of a powerful cosmological observable.

Frequency multiplexed superconducting quantum interference device readout of large bolometer arrays for cosmic microwave background measurements.

A technological milestone for experiments employing transition edge sensor bolometers operating at sub-Kelvin temperature is the deployment of detector arrays with 100s-1000s of bolometers. One key technology for such arrays is readout multiplexing: the ability to read out many sensors simultaneously on the same set of wires. This paper describes a frequency-domain multiplexed readout system which has been developed for and deployed on the APEX-SZ and South Pole Telescope millimeter wavelength receivers. In this system, the detector array is divided into modules of seven detectors, and each bolometer within the module is biased with a unique ∼MHz sinusoidal carrier such that the individual bolometer signals are well separated in frequency space. The currents from all bolometers in a module are summed together and pre-amplified with superconducting quantum interference devices operating at 4 K. Room temperature electronics demodulate the carriers to recover the bolometer signals, which are digitized separately and stored to disk. This readout system contributes little noise relative to the detectors themselves, is remarkably insensitive to unwanted microphonic excitations, and provides a technology pathway to multiplexing larger numbers of sensors.

Invited article: millimeter-wave bolometer array receiver for the Atacama pathfinder experiment Sunyaev-Zel'dovich (APEX-SZ) instrument.

The Atacama pathfinder experiment Sunyaev-Zel'dovich (APEX-SZ) instrument is a millimeter-wave cryogenic receiver designed to observe galaxy clusters via the Sunyaev-Zel'dovich effect from the 12 m APEX telescope on the Atacama plateau in Chile. The receiver contains a focal plane of 280 superconducting transition-edge sensor (TES) bolometers instrumented with a frequency-domain multiplexed readout system. The bolometers are cooled to 280 mK via a three-stage helium sorption refrigerator and a mechanical pulse-tube cooler. Three warm mirrors, two 4 K lenses, and a horn array couple the TES bolometers to the telescope. APEX-SZ observes in a single frequency band at 150 GHz with 1' angular resolution and a 22' field-of-view, all well suited for cluster mapping. The APEX-SZ receiver has played a key role in the introduction of several new technologies including TES bolometers, the frequency-domain multiplexed readout, and the use of a pulse-tube cooler with bolometers. As a result of these new technologies, the instrument has a higher instantaneous sensitivity and covers a larger field-of-view than earlier generations of Sunyaev-Zel'dovich instruments. The TES bolometers have a median sensitivity of 890 µK(CMB)√s (NEy of 3.5 × 10(-4) √s). We have also demonstrated upgraded detectors with improved sensitivity of 530 µK(CMB)√s (NEy of 2.2 × 10(-4) √s). Since its commissioning in April 2007, APEX-SZ has been used to map 48 clusters. We describe the design of the receiver and its performance when installed on the APEX telescope.

Mitochondrial neurogastrointestinal encephalomyopathy syndrome maps to chromosome 22q13.32-qter.

Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) syndrome is a rare, multisystem disorder characterized clinically by ptosis, progressive external ophthalmoplegia, gastrointestinal dysmotility, leukoencephalopathy, thin body habitus, and myopathy. Laboratory studies reveal defects of oxidative-phosphorylation and multiple mtDNA deletions frequently in skeletal muscle. We studied four ethnically distinct families affected with this apparently autosomal recessive disorder. Probands from each family were shown, by Southern blot, to have multiple mtDNA deletions in skeletal muscle. We mapped the MNGIE locus to 22q13.32-qter, distal to D22S1161, with a maximum two-point LOD score of 6.80 at locus D22S526. Cosegregation of MNGIE with a single chromosomal region in families with diverse ethnic backgrounds suggests that we have mapped an important locus for this disorder. We found no evidence to implicate three candidate genes in this region, by using direct sequence analysis for DNA helicase II and by assaying enzyme activities for arylsulfatase A and carnitine palmitoyltransferase.

Human immunodeficiency virus wasting syndrome may represent a treatable myopathy.

We evaluated 5 patients with the diagnosis of HIV wasting syndrome. None had severe diarrhea or other causes for malabsorption. All had myopathy by clinical, laboratory, and muscle biopsy criteria. Withdrawal of azidothymidine in 3 patients did not lead to improvement. Corticosteroid therapy was effective in 3 patients.

Human immunodeficiency virus-associated myopathy: analysis of 11 patients.

Neuromuscular disorders reported in association with human immunodeficiency virus (HIV) infection include several forms of peripheral neuropathy and polymyositis. We report 11 patients with HIV-associated myopathy. Five patients with acquired immunodeficiency syndrome (AIDS), 2 with AIDS-related complex, and 4 otherwise asymptomatic HIV-infected patients developed progressive proximal muscle weakness. Serum creatine phosphokinase levels were elevated and electromyography revealed abnormal spontaneous activity and myopathy in most patients. All 8 muscle biopsy specimens showed fiber necrosis. Four had inflammatory infiltrates, and nemaline rod bodies were prominent in 3. Immunosuppressant therapy in 5 patients resulted in improvement. Attempts at viral localization in 4 muscle biopsy specimens were unsuccessful. These findings suggest a distinct association between HIV infection and myopathy with features atypical for polymyositis.

Clinical experience in more than 2000 patients with myasthenia gravis.

The vast strides in terms of pathophysiologic understanding which have been made in the past 25 years of research in myasthenia gravis are remarkable. This period of time has also seen the evolution of many applicable technological advances to better our care of these patients. Myasthenia's place in the autoimmune family of diseases has been demonstrated. No clear-cut strategy resulting from these discoveries has, however, been more than one of temporary relief or clinical improvement. In our center over these years the performance of early thymectomy in all cases of generalized myasthenia seems to be the one demonstrably reliable technique available. The effect of this procedure on coexisting neoplasia and other autoimmune disease suggests continuing avenues of investigation.

Autonomic neuropathy associated with autoimmune disease.

Mononeuropathy multiplex and mixed sensorimotor neuropathy are known complications of systemic vasculitis and related autoimmune disorders. Autonomic dysfunction is not generally considered a neurologic complication of these diseases. We report two patients who came to neurologic attention because of autonomic dysfunction and were then discovered to have autoimmune disease. Autonomic dysfunction may be the presenting sign of autoimmune disorders, which should be considered in the differential diagnosis of acquired autonomic disturbances.

Muscle phosphofructokinase deficiency. Biochemical and immunological studies of phosphofructokinase isozymes in muscle culture.

Muscle cultures from three unrelated patients with muscle phosphofructokinase (PFK; EC 2.7.1.11) deficiency (Glycogenosis type VII; Tarui disease) had normal PFK activity and normal morphology. Chromatographic and immunological studies showed that normal muscle cultures express all three PFK subunits, M (muscle-type), L (liver-type), and P (platelet-type) and contain multiple homotetrameric and heterotetrameric isozymes. Muscle cultures from patients lack catalytically active M subunit-containing isozymes, but this is compensated for by the presence of P- and L-containing isozymes. Despite the lack of muscle-type PFK activity, presence of immunoreactive M subunit was demonstrable by indirect immunofluorescence, suggesting a mutation of the structural gene coding for the M-subunit of PFK.

Isaacs' syndrome with muscle hypertrophy reversed by phenytoin therapy.

A 16-year-old boy was seen for severe episodic muscle cramps and generalized myokymia, consistent with Isaacs's syndrome. Bilateral calf hypertrophy (46-cm calf circumference) and ankle areflexia were noted. He was treated with phenytoin sodium, 300 mg/day. Within three months there was marked decrease in myokymia, total relief of cramps, return of ankle reflexes, and 6-cm reduction in calf circumference. We suggest that the excess muscle activity in Isaacs's syndrome may be responsible for the associated phenomena of muscle hypertrophy and areflexia.

Hypokalemic periodic paralysis exacerbated by acetazolamide.

Although acetazolamide usually prevents paralytic attacks in hypokalemic periodic paralysis, not all patients benefit from this treatment. We studied a father and two sons in whom attack frequency and severity increased on acetazolamide. Administration of triamterene virtually abolished attacks in three separate single-blind trials totaling more than 12 months. Spontaneous and glucose-insulin provoked occurred with only slight hypokalemia. Acetazolamide produced slight hypokalemia and provoked attacks of weakness whereas triamterene increased potassium levels significantly. Certain patients with hypokalemic periodic paralysis are worsened by acetazolamide, perhaps because of its kaliopenic effect. Triamterene may be effective in some of these patients.

Acetylcholine receptor antibodies in myasthenia gravis.

A multivariate statistical analysis of levels of serum acetylcholine receptor antibody (AChR Ab) obtained from 197 patients with various clinical forms of myasthenia gravis (MG) was performed. Elevated AChR Ab levels are specific for MG, but normal AChR Ab levels do not rule out MG. Patients in remission or with purely ocular MG had the lowest incidence of elevation of serum AChR Ab levels, while patients with generalized, severe MG, particularly in the presence of thymoma, tended to have the greatest antibody elevations. Corticosteroids depressed AChR Ab levels, but thymectomy did not exert a consistent effect on antibody levels within a 24- to 30-month postoperative period. The relatively low 55% positivity of antibody elevations in all 197 patients probably reflects the use of heterologous (rat) AChR.

Plasmapheresis in refractory generalized myasthenia gravis.

A group of 16 patients with severe generalized myasthenia gravis (MG) (five with thymoma) that was resistant to anticholinesterases, thymectomy, and corticosteroids were treated by plasmapheresis. Twelve patients showed an excellent clinical response. Plasmapheresis is an effective treatment modality for many patients with severe generalized MG resistant to other forms of therapy. Unfortunately, the beneficial results are only transient and periodic plasmapheresis treatments are necessary.

Chronic GM2 gangliosidosis masquerading as atypical Friedreich ataxia: clinical, morphologic, and biochemical studies of nine cases.

A progressive spinocerebellar degenerative disorder was characterized in nine patients, aged 11 to 37 years, from four unrelated Ashkenazi Jewish families; affected individuals had markedly deficient beta-hexosaminidase A activity. Symptoms included early onset of cerebellar signs (tremor, incoordination, and dysarthia) and, with maturity, the development of upper and lower motor neuron disorders, marked dysarthia, and ataxia. Three older patients, aged 26, 32, and 37 years, had dementia or recurrent psychotic episodes. Membrane-bound lamellar cytoplasmic inclusions, consistent with lysosomal ganglioside accumulation, were observed in rectal ganglia. The activity of beta-hexosaminidase A was markedly deficient in all sources analyzed. Parents had activities consistent with heterozygosity, confirming autosomal-recessive transmission of the beta-hexosaminidase A-deficient gene and the adult variant disorder. Residual beta-hexosaminidase A activity, partially purified by anion-exchange chromatography from cultured skin fibroblasts of the affected individuals, was heat-labile and co-electrophoresed with normal beta-hexosaminidase A. These findings suggest that these patients were allelic for a new beta-hexosaminidase A mutation and may represent a genetic compound of this allele and the allele causing Tay-Sachs disease.

Methioninemia and myopathy: a new disorder.

A 7 1/2-year-old girl with hypermethioninemia, myopathy, and mental deficiency (IQ = 65) is described. The increased methionine was not associated with deficiency of methionine adenosyltransferase, which was normal or increased in liver, muscle, erythrocytes, and cultured fibroblasts. Methionyl-tRNA synthetase in fibroblasts was normal. The hypermethioninemia and a concurrently increased blood S-adenosylmethionine declined on a diet low in methionine. There was a diffuse, symmetrical, moderate proximal muscle weakness, but muscle atrophy was not discernible, and the deep tendon reflexes were hypoactive but obtainable. Electromyographic abnormalities were not detected. Electron microscopy of muscle revealed 3 to 6 small myelin figures in the region of the I band in nearly every fiber, with occasional myelin figures at other sites also. These myelin figures were more numerous and smaller than those seen accompanying nonspecific myopathies and may reflect a more specific pathological change. Electron microscopy of liver revealed three nonspecific lesions in all hepatocytes: (1) numerous megamitochondria with crystalloid deposit in the matrix; (2) increased numbers of small vesicles of smooth endoplasmic reticulum; and (3) loss of plasma membrane microvilli, with extensive bleb formation and shedding of cytoplasm into Disse's space.

Amaurosis fugax associated with ophthalmic artery stenosis: clinical simulation of carotid artery disease.

A 72 year old woman complained of transient loss of vision in the left eye. She had undergone a left carotid endarterectomy 10 years previously. Reduced ophthalmic artery pressure was found on noninvasive carotid artery testing and cerebral angiography was performed. No lesion was evident in the carotid artery, but significant ophthalmic artery stenosis was identified. We report this case as showing the occurrence of amaurosis fugax in association with ophthalmic artery stenosis.