Exascale integrated modeling of low-order wavefront sensing and control for the Roman Coronagraph instrument.

Astronomical instruments to detect exoplanets require extreme wavefront stability. For these missions to succeed, comprehensive and precise modeling is required to design and analyze suitable coronagraphs and their wavefront control systems. In this paper, we describe techniques for integrated modeling at scale that is, to the best of our knowledge, 1000 times faster than previously published works. We show how this capability has been used to validate performance and perform uncertainty quantification for the Roman Coronagraph instrument. Finally, we show how this modeling capacity may be necessary to design and build the next generation of space-based coronagraph instruments.

Correlation of MRI Appearance of Autologous Chondrocyte Implantation in the Ankle with Clinical Outcome.

The objective of this study was to characterize magnetic resonance imaging (MRI) findings and correlate with clinical results in patients who underwent autologous chondrocyte implantation (ACI) of osteochondral lesions of the talus (OLT). METHODS: Twenty-four grafts were evaluated at a mean 65.8 months after ACI for OLT. MRI was performed on a 1.5-T GE scanner using multiple sequences. Graft appearance was compared with preoperative MRI and evaluated for 6 criteria: defect fill, surface regularity, signal pattern, bone marrow edema, subchondral plate irregularity, and presence of cystic lesions. Clinical outcome was measured with the American Orthopaedic Foot and Ankle Society (AOFAS) clinical outcome score. RESULTS: Of 24 grafts, 22 (92%) demonstrated >75% defect fill. Eighteen (75%) had a mildly irregular and 6 (25%) had a moderately irregular articular surface. The signal pattern of the repair tissue was heterogenous in 23 (96%); 14 (58%) layered and 9 (38%) mottled. Fourteen grafts (58%) showed decreased amount of bone marrow edema while 4 (17%) had no change and 5 (21%) had an increase in the amount of bone marrow edema. The subchondral bone plate was abnormal in most grafts, with focal defects seen in 10, slight depression in 7, and both in 5. Seven had an increase in cystic lesions while the others had no change, decrease or no cysts seen. Mean postoperative AOFAS score was 87.5 with mean improvement of 39.4. CONCLUSIONS: At 66-month mean follow-up, MRI appearance of the ACI grafts show imaging abnormalities but demonstrate good clinical results. While MRI is an important tool in the postoperative assessment of ACI grafts, the various variations from a normal/nonoperative ankle must be interpreted with caution.

Autologous chondrocyte implantation of the ankle: 2- to 10-year results.

BACKGROUND: The treatment of osteochondral lesions of the talus after failed surgery is challenging, with no clear solution. Short-term results using autologous chondrocyte implantation have been promising. PURPOSE: To report the long-term outcomes of patients who underwent autologous chondrocyte implantation (ACI) of the talus after failed marrow stimulation techniques for osteochondral lesions of the talus (OLTs). STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Thirty-two consecutive patients underwent ACI of the talus, and 29 patients (15 male, 14 female; mean age, 34 years [range, 16-54 years]) were available for follow-up. There were 23 medial and 6 lateral lesions, with a mean size of 18 × 11 mm (198 mm(2); range, 80-500 mm(2)). Twenty patients underwent ACI of the talus alone; 9 underwent ACI with bone grafting of underlying cysts. Follow-up was performed at a mean of 70 months (range, 24-129 months). Patient outcomes were evaluated using the simplified symptomatology score, Tegner activity score, Finsen score, and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score. Twenty-five patients (86%) underwent second-look arthroscopic surgery at the time of hardware removal and were assessed with the International Cartilage Repair Society (ICRS) score. Postoperative magnetic resonance imaging (MRI) was performed on 24 patients (83%) and compared with preoperative MRI scans. RESULTS: Preoperatively, 26 patients rated their ankles as poor and 3 as fair using the simplified symptomatology score. At last follow-up, 9 were classified as excellent, 14 as good, 5 as fair, and 1 as poor using the same score. The mean AOFAS score improved from 50.1 to 85.9 (range, 65-100). The mean Tegner activity score improved from 1.6 to 4.3 (P < .0001). The mean Finsen score (modified Weber score) showed significant improvement from 13.7 to 5.1 (P < .0001). CONCLUSION: Autologous chondrocyte implantation of the talus yields improvement in all parameters tested with enduring long-term results in patients who have failed previous surgery for OLTs.

Role of FYN kinase in spermatogenesis: defects characteristic of Fyn-null sperm in mice.

FYN kinase is highly expressed in the testis and has been implicated in testis and sperm function, yet specific roles for this kinase in testis somatic and germ cells have not been defined. The purpose of the present investigation was to identify aspects of spermatogenesis, spermiation, or sperm fertilizing capacity that required FYN for normal reproductive function. Matings between Fyn-null males and wild-type females resulted in normal litter sizes, despite the fact that Fyn-null males exhibited reduced epididymal size and sperm count. Morphological analysis revealed a high frequency of abnormal sperm morphology among Fyn-null sperm, and artificial insemination competition studies demonstrated that Fyn-null sperm possessed reduced fertilizing capacity. Fyn-null sperm exhibited nearly normal motility during capacitation in vitro but reduced ability to undergo the acrosome reaction and fertilize oocytes. The typical pattern of capacitation-induced protein tyrosine phosphorylation was slightly modified in Fyn-null sperm, with reduced abundance of several minor phosphoproteins. These findings are consistent with a model in which FYN kinase plays an important role in proper shaping of the head and acrosome within the testis and possibly an additional role in the sperm acrosome reaction, events required for development of full fertilizing capacity in sperm.

Surgical treatment of osteochondral lesions of the talus.

When conservative treatment is unsuccessful, there are many surgical options to treat patients with symptomatic chronic osteochondral lesions of the talus. The chosen treatment depends on the patient's symptoms, clinical examination findings, preoperative imaging results, and whether prior surgery was unsuccessful. It is important to be aware of treatment alternatives such as marrow stimulation, osteochondral autograft or allograft plugs, autologous chondrocyte implantation, and newer techniques currently being investigated outside the United States.

Effect of bone cement viscosity and set time on mantle area in total knee arthroplasty.

To assess the impact of bone cement viscosity on total knee arthroplasty, we compared 1 high-viscosity and 2 medium-viscosity cements with respect to mantle area and zone-specific intrusion depths into the tibial plateau. We analyzed postoperative radiographs to determine penetration area and depth in 72 consecutive patients (79 knees) in whom DePuy II (n = 11), Endurance (n = 34), or Simplex-P (n = 34) cement was used. Penetration into the tibial plateau (anteroposterior zones 1-4) was significantly reduced with use of the high-viscosity DePuy II cement but did not differ significantly between the 2 medium-viscosity cements, Endurance and Simplex-P. Surgical and tourniquet times were significantly decreased with the quicker setting DePuy II cement. Given these findings, additional studies are warranted to assess the long-term impact of the lower intrusion depths found with DePuy II cement. Such differences in cement penetration could jeopardize long-term fixation and lead to higher long-term device failure rates.

CC12, a high-affinity ligand for [3H]cimetidine binding, is an improgan antagonist.

Improgan, a chemical congener of cimetidine, is a highly effective non-opioid analgesic when injected into the CNS. Despite extensive characterization, neither the improgan receptor, nor a pharmacological antagonist of improgan has been previously described. Presently, the specific binding of [(3)H]cimetidine (3HCIM) in brain fractions was used to discover 4(5)-((4-iodobenzyl)thiomethyl)-1H-imidazole, which behaved in vivo as the first improgan antagonist. The synthesis and pharmacological properties of this drug (named CC12) are described herein. In rats, CC12 (50-500nmol, i.c.v.) produced dose-dependent inhibition of improgan (200-400nmol) antinociception on the tail flick and hot plate tests. When given alone to rats, CC12 had no effects on nociceptive latencies, or on other observable behavioral or motor functions. Maximal inhibitory effects of CC12 (500nmol) were fully surmounted with a large i.c.v. dose of improgan (800nmol), demonstrating competitive antagonism. In mice, CC12 (200-400nmol, i.c.v.) behaved as a partial agonist, producing incomplete improgan antagonism, but also limited antinociception when given alone. Radioligand binding, receptor autoradiography, and electrophysiology experiments showed that CC12's antagonist properties are not explained by activity at 25 sites relevant to analgesia, including known receptors for cannabinoids, opioids or histamine. The use of CC12 as an improgan antagonist will facilitate the characterization of improgan analgesia. Furthermore, because CC12 was also found presently to inhibit opioid and cannabinoid antinociception, it is suggested that this drug modifies a biochemical mechanism shared by several classes of analgesics. Elucidation of this mechanism will enhance understanding of the biochemistry of pain relief.

Antinociceptive activity of chemical congeners of improgan: optimization of side chain length leads to the discovery of a new, potent, non-opioid analgesic.

Improgan is a chemical congener of the H2 antagonist cimetidine which shows the profile of a highly effective analgesic when administered directly into the CNS. Although the improgan receptor is unknown, improgan activates analgesic pathways which are independent of opioids, but may utilize cannabinoid mechanisms. To discover selective, potent, improgan-like drugs, seven compounds chemically related to improgan were synthesized and tested for antinociceptive activity in rats after intracerebroventricular (icv) administration. Among a series of improgan congeners in which the alkyl chain length of improgan ((-CH2)3-) was varied, five compounds showed full agonist antinociceptive activity with potencies greater than that of improgan. VUF5420 (containing (-CH2)4-, EC50 = 86.1 nmol) produced maximal antinociceptive activity after doses which showed no motor impairment or other obvious toxicity, and was 2.3-fold more potent than improgan (EC50 = 199.5 nmol). As found previously with improgan, VUF5420-induced antinociception was unaffected by administration of the opioid antagonist naltrexone, but was inhibited by the CB1 antagonist SR141716A, suggesting a non-opioid, cannabinoid-related analgesic action. However, VUF5420 showed very low affinity (Kd approximately 10 microM) on CB1-receptor activation of 35S-GTPgammaS binding, indicating that this drug does not directly interact with the CB1 receptor in vivo. The present results show that VUF5420 is a high potency, improgan-like, non-opioid analgesic which may indirectly activate cannabinoid pain-relieving mechanisms.

Imaging through turbulence with a quadrature-phase optical interferometer.

We present an improved technique for imaging through turbulence at visible wavelengths using a rotation shearing pupil-plane interferometer, intended for astronomical and terrestrial imaging applications. While previous astronomical rotation shearing interferometers have made only visibility modulus measurements, this interferometer makes four simultaneous measurements on each interferometric baseline, with phase differences of pi/2 between each measurement, allowing complex visibility measurements (modulus and phase) across the entire input pupil in a single exposure. This technique offers excellent wavefront resolution, allowing operation at visible wavelengths on large apertures, is potentially immune to amplitude fluctuations (scintillation), and may offer superior calibration capabilities to other imaging techniques. The interferometer has been tested in the laboratory under weakly aberrating conditions and at Palomar Observatory under ordinary astronomical observing conditions. This research is based partly on observations obtained at the Hale Telescope.