Frequency-Dependent Squeezed Vacuum Source for the Advanced Virgo Gravitational-Wave Detector.

In this Letter, we present the design and performance of the frequency-dependent squeezed vacuum source that will be used for the broadband quantum noise reduction of the Advanced Virgo Plus gravitational-wave detector in the upcoming observation run. The frequency-dependent squeezed field is generated by a phase rotation of a frequency-independent squeezed state through a 285 m long, high-finesse, near-detuned optical resonator. With about 8.5 dB of generated squeezing, up to 5.6 dB of quantum noise suppression has been measured at high frequency while close to the filter cavity resonance frequency, the intracavity losses limit this value to about 2 dB. Frequency-dependent squeezing is produced with a rotation frequency stability of about 6 Hz rms, which is maintained over the long term. The achieved results fulfill the frequency dependent squeezed vacuum source requirements for Advanced Virgo Plus. With the current squeezing source, considering also the estimated squeezing degradation induced by the interferometer, we expect a reduction of the quantum shot noise and radiation pressure noise of up to 4.5 dB and 2 dB, respectively.

Search for Subsolar-Mass Binaries in the First Half of Advanced LIGO's and Advanced Virgo's Third Observing Run.

We report on a search for compact binary coalescences where at least one binary component has a mass between 0.2 M_{⊙} and 1.0 M_{⊙} in Advanced LIGO and Advanced Virgo data collected between 1 April 2019 1500 UTC and 1 October 2019 1500 UTC. We extend our previous analyses in two main ways: we include data from the Virgo detector and we allow for more unequal mass systems, with mass ratio q≥0.1. We do not report any gravitational-wave candidates. The most significant trigger has a false alarm rate of 0.14 yr^{-1}. This implies an upper limit on the merger rate of subsolar binaries in the range [220-24200] Gpc^{-3} yr^{-1}, depending on the chirp mass of the binary. We use this upper limit to derive astrophysical constraints on two phenomenological models that could produce subsolar-mass compact objects. One is an isotropic distribution of equal-mass primordial black holes. Using this model, we find that the fraction of dark matter in primordial black holes in the mass range 0.2 M_{⊙}

Fabrication and mechanical characterization of 3D electrospun scaffolds for tissue engineering.

Electrospinning is a polymer processing technique that produces fibrous structures comparable to the extracellular matrix of many tissues. Electrospinning, however, has been severely limited in its tissue engineering capabilities because this technique has produced few three-dimensional structures. Sintering of electrospun materials provides a method to fabricate unique architectures and allow much larger structures to be made. Electrospun mats were sintered into strips and cylinders, and their tensile and compressive mechanical properties were measured. In addition, electrospun materials with salt pores (salt embedded within the material and then leached out) were fabricated to improve porosity of the electrospun materials for tissue engineering scaffolds. Sintered electrospun poly(D,L-lactide) and poly(L-lactide) (PDLA/PLLA) materials have higher tensile mechanical properties (modulus: 72.3 MPa, yield: 960 kPa) compared to unsintered PLLA (modulus: 40.36 MPa, yield: 675.5 kPa). Electrospun PDLA/PLLA cylinders with and without salt-leached pores had compressive moduli of 6.69 and 26.86 MPa, respectively, and compressive yields of 1.36 and 0.56 MPa, respectively. Sintering of electrospun materials is a novel technique that improves electrospinning application in tissue engineering by increasing the size and types of electrospun structures that can be fabricated.

Poor prognosis acute myelogenous leukemia: 1 - response to treatment with high dose cytarabine/mitoxantrone/ethyol @ (Amifostine).

Twenty patients with poor prognosis AML and four patients in the blastic phase of a myeloproliferative disorder were treated with two 'pulses' of therapy each consisting of two doses of high dose araC (separated by 12 h) followed by a single dose of mitoxantrone. The pulses were separated by 96 h. Amifostine was then administered tiw. The median age of the population was 68 years with 88% of patients having had either a prior MDS, MPD or toxic exposure. The acute leukemia of 58% of patients either entered a CR or reverted to preleukemic state. For patients under 70 years of age, treatment produced 62% CRs with a leukemia free decision marrow in 77%. For patients over 70 years the CR rate was 27% with 36% of patients having a leukemia free decision marrow.

Patients with myelodysplastic syndromes benefit from palliative therapy with amifostine, pentoxifylline, and ciprofloxacin with or without dexamethasone.

Thirty-five patients with myelodysplastic syndrome (MDS) were registered on protocol MDS 96-02 and were receiving continuous therapy with pentoxifylline 800 mg 3 times a day and ciprofloxacin 500 mg twice a day by mouth; dexamethasone was added to the regimen for the partial responders and the nonresponders after 12 weeks at a dose of 4 mg by mouth every morning for 4 weeks. Amifostine was administered intravenously 3 times a week at 3 dose levels (200 mg/M(2), 300 mg/M(2), and 400 mg/M(2)) to cohorts of 10 patients each. Therapy has been continued for 1 year in responders. Twenty-nine have completed at least 12 weeks of therapy and are available for response evaluation. Of the 21 men and 8 women (median age, 67 years), 20 had refractory anemia (RA), 3 had RA with ringed sideroblasts (RARS), 5 had RA with excess blasts (RAEB), and 1 had chronic myelomonocytic leukemia (CMMoL). Five had secondary MDS. No differences were noted in response rates among the 3 dose levels. Seven patients did not respond at all, and 22 showed an improvement in cytopenias (76%). Three had a triple lineage response, 10 had a double lineage response, and 9 had a single lineage response (8 of 9 in absolute neutrophil count [ANC] and 1 had more than a 50% reduction in packed red blood cell transfusions). Fifteen patients responded only after the addition of dexamethasone, whereas 7 responded before. When examined by lineage, 19 of 22 showed improved ANC, 11 of 22 demonstrated more than 50% reduction in blood transfusions, improved Hb levels, or both, and 7 of 22 showed improvement in platelet counts. Interestingly, the responses were frequently slow to appear, and continued improvement in counts was seen up to 12 months of therapy and beyond. This study supports the feasibility of treating patients with MDS with the unique approach of cytoprotection and anticytokine therapies as well as the principle that prolonged commitment to treatment is desirable when noncytotoxic agents are administered. (Blood. 2000;95:1580-1587)

Biologic characteristics of 164 patients with myelodysplastic syndromes.

Rates of proliferation, apoptosis and cytokine expression were measured in bone marrow (BM) biopsies of 164 myelodysplastic syndrome (MDS) patients. There were 107 males and 57 females. Median age was 69 years and 101 had refractory anemia (RA), 17 RA with ringed sideroblasts (RARS), 38 with RA and excess blasts (RAEB) and 8 with RAEB in transformation (RAEB-t). Apoptosis measured by in-situ end labeling (ISEL) was directly related to the number of macrophages (p = 0.028, n = 83). Mean tumor necrosis factor alpha (TNF-alpha) and ISEL positivity were higher in RAEB + RAEB-t patients (p = 0.0554 and p = 0.06 respectively) while hemoglobin was higher for RA + RARS group (p = 0.0472). Patients with high apoptosis had lower white blood cell counts (p = 0.0009), lower percentage of blasts (p = 0.0009) and higher number of macrophages (p = 0.0086). We conclude that measurements of apoptosis, proliferation and cytokine expression provide important biological information which helps to distinguish RA + RARS patients from RAEB + RAEB-t patients, and may be of additive prognostic significance.

Biological characteristics of myelodysplastic syndrome patients who demonstrated high versus no intramedullary apoptosis.

Spontaneous intramedullary apoptosis was measured in bone marrow (BM) biopsies of 175 patients with myelodysplastic syndromes (MDS) using in situ end-labeling (ISEL) of fragmented DNA. Two groups of high (n=71) versus low (n =43) levels of apoptosis were identified while 61 patients were ISEL-negative. Semiquantitative assessment of 3 cytokines, the number of macrophages and in vivo labeling indices (LI) were also determined from consecutive sections of the biopsy. Patients with high apoptosis levels tended to have a high LI (p=0.013), more macrophages in their BM biopsies (p=0.006) and higher tumor necrosis factor alpha (TNF-alpha) levels (not significant) compared to patients with no apoptosis. In addition, low risk MDS patients had significantly lower rates of apoptosis (p = 0.047) and lower levels of TNF-alpha (p = 0.055) compared to high-risk MDS patients. We conclude that the genesis of cytopenias in MDS is of multifactorial origin and that cytokine-associated apoptosis clearly identifies a distinct biological subgroup of patients who may benefit selectively by use of anti-cytokine therapies.