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Variability assessment of qualitative data has an important role in diverse areas such as sociology, quality engineering, healthcare, decision making, genetics, metrology in chemistry and many others. To test the homogeneity hypothesis, we use two main categorical factors. Using a cross-balanced design, we provide a decomposition theorem of the sample total-variation into ‘intra’ (within) component and ‘inter’ (between) component for any scale. Building on this, we provide a way for decomposing the ‘inter’ component itself into variation components contributed by the two factors and their interaction (when we consider more than one replicated test in the cross-design). Moreover, focusing on an ordinal scale, we offer segregation power indices for testing the significate effects of the two factors and their interaction. A two-way ORDANOVA calculator is provided to display the empirical distributions of the segregation power indices and to find critical points of the test statistics distributions at the given confidence level. Some examples are given to demonstrate the proposed method.

In a conventional radar system, the hardware cost increases with the sampling rate of the receiver. Sub‐Nyquist radar systems operate at lower sampling rates and hence reduce the hardware cost and complexity. A sub‐Nyquist radar system uses the knowledge of the transmit pulse shape to determine the targets. However, the pulse shape is often distorted in practice and unknown to the receiver. An alternative sub‐Nyquist radar system that uses multiple receiver was proposed that estimates the targets without knowledge of the pulse shape. In this demo, the authors build a hardware prototype to demonstrate the proposed multi‐receiver sub‐Nyquist radar. The proposed two‐receiver system with an unknown pulse has comparable pre‐forms to a conventional sub‐Nyquist system is shown. This paper shows a hardware demonstration of sub‐Nyquist sampling of finite‐rate‐of‐innovation signals when the basic pulse shape is unknown. The results are particularly interesting in radar imaging, where the transmit pulse is distorted while propagation and unknown at the receiver.

Lasers and especially semiconductor lasers (SCLs) are playing a major role in advanced technological and scientific tasks ranging from sensing, fundamental investigations in quantum optics and communications. The demand for ever-increasing accuracy and communication rates has driven these applications to employ phase modulation and coherent detection. The main laser attribute that comes into play is its coherence which is usually quantified by either the Schawlow-Townes (S-T) linewidth, the spectral width of the laser field, or the power spectral density (PSD) function of the laser frequency fluctuation. In this paper, we present a derivation of a general and direct relationship between these two coherence measures. We refer to the result as the Central Relation. The relation applies independently of the physical origin of the noise. Experiments are described which demonstrate the validity of the Central Relation and at the same time suggest new methods of controlling frequency noise at base band by optical filtering.

As a result of field fringing, the capacitance of a parallel-plate capacitor differs from that predicted by the textbook formula. Using singular perturbations and conformal mapping techniques, we calculate the leading-order correction to the capacitance in the limit of large aspect ratio. We additionally obtain a comparable approximation for the electrostatic attraction between the plates.

BACKGROUND Visual and acoustic virtual reality (VR) has been increasingly explored as a non-pharmacological tool for pain relief in clinical settings. OBJECTIVE We aimed to evaluate the effectiveness of VR as a distraction technique in the management of acute pain during operative hysteroscopy in the outpatient setting. METHODS A prospective, open-label, randomized control trial in a tertiary university-affiliated medical centre between April and August 2020. Overall, 82 women were randomly allocated to undergo operative hysteroscopy either with the use of VR (n = 44, study group) or with standard treatment (control group, n = 38). VR was applied throughout the procedure and no anaesthesia was given. The primary outcome measures included self-reported intraoperative pain. Other objectives included vital parameters as pulse rate (PR) and respiratory rate (RR) before and during the first 3 min of the procedure. Pain and anxiety outcomes were measured as numeric rating scores. RESULTS The baseline parameters were similar between groups. The mean duration for the procedure was 8.1 ± 3.2 vs. 7.3 ± 6.0 min for the study and the control groups (p = 0.23). There were no statistically significant differences between the reported pain scores during the procedure [median (interquartile range) 5.0 (3.0-7.2) vs. 5.0 (3.0-8.0), respectively; p = 0.67]. While neither intraoperative heart rate nor respiratory rate differed between groups [14.0 (13.0-16.0) vs. 14.0 (11.0-16.5); p = 0.77)], the increase of heart rate was found greater in the VR group [+7.0 (8.5) vs. +1.0 (12.2); p = 0.01]. CONCLUSION VR was not effective in reducing pain during an outpatient operative hysteroscopy. SIGNIFICANCE The use of a Virtual reality system was found ineffective in reducing pain during and after an office operative hysteroscopy without anaesthesia, in a thorough examination of both continuous physiological parameters and women's self-reported measures.

We have recently introduced a new semiconductor laser design which is based on an extreme, 99%, reduction of the laser mode absorption losses. In previous reports, we showed that this was achieved by a laser mode design which confines the great majority of the modal energy (> 99%) in a low-loss Silicon guiding layer rather than in highly-doped, thus lossy, III–V p$${}^+$$ + and n$${}^+$$ + layers, which is the case with traditional III–V lasers. The resulting reduced electron-field interaction was shown to lead to a commensurate reduction of the spontaneous emission rate by the excited conduction band electrons into the laser mode and thus to a reduction of the frequency noise spectral density of the laser field often characterized by the Schawlow–Townes linewidth. In this paper, we demonstrate theoretically and present experimental evidence of yet another major beneficial consequence of the new laser design: a near total elimination of the contribution of amplitude-phase coupling (the Henry $$\alpha $$ α parameter) to the frequency noise at “high” frequencies. This is due to an order of magnitude lowering of the relaxation resonance frequency of the laser. Here, we show that the practical elimination of this coupling enables yet another order of magnitude reduction of the frequency noise at high frequencies, resulting in a quantum-limited frequency noise spectral density of 130 Hz$$^2$$ 2 /Hz (linewidth of 0.4 kHz) for frequencies beyond the relaxation resonance frequency 680 MHz. This development is of key importance in the development of semiconductor lasers with higher coherence, particularly in the context of integrated photonics with a small laser footprint without requiring any sort of external cavity.

In this paper, we propose and demonstrate a solution to the problem of coherence degradation and collapse caused by the back reflection of laser power into the laser resonator. The problem is most onerous in semiconductor lasers (SCLs), which are normally coupled to optical fibers, and results in the fact that practically every commercial SCL has appended to it a Faraday-effect isolator that blocks most of the reflected optical power preventing it from entering the laser resonator. The isolator assembly is many times greater in volume and cost than the SCL itself. This problem has resisted a practical and economic solution despite decades of effort and remains the main obstacle to the emergence of a CMOS-compatible photonic integrated circuit technology. A simple solution to the problem is thus of major economic and technological importance. We propose a strategy aimed at weaning semiconductor lasers from their dependence on external isolators. Lasers with large internal Q-factors can tolerate large reflections, limited only by the achievable Q values, without coherence collapse. A laser design is demonstrated on the heterogeneous Si/III-V platform that can withstand 25 dB higher reflected power compared to commercial DFB lasers. Larger values of internal Qs, achievable by employing resonator material of lower losses and improved optical design, should further increase the isolation margin and thus obviate the need for isolators altogether.

Peronospora belbahrii is one of the most destructive downy mildew diseases that has emerged throughout the past two decades. Due to the lack of quarantine regulations and its possible seed-borne nature, it has spread globally and is now present in most areas in which basil is produced. While most obligate biotrophic, plant parasitic oomycetes are highly host-specific, there are a few that have a wider host range, e.g. Albugo candida, Bremia tulasnei, and Pseudoperonospora cubensis. Recently, it was shown that Peronospora belbahrii is able to infect Rosmarinus, Nepetia, and Micromeria in Israel in cross-infection trials, hinting an extended host range for also this pathogen. In this study, a newly occurring downy mildew pathogen on lavender was investigated with respect to its morphology and phylogeny, and it is shown that it belongs to Peronospora belbahrii as well. Thus, it seems that Peronospora belbahrii is currently extending its host range to additional members of the tribe Mentheae and Ocimeae. Therefore, it seems advisable to scrutinise all commonly used members of these tribes in order to avoid further spread of virulent genotypes.

Coherent optical communication is considered as an indispensable solution to the ever-increasing demand for higher data rates. To reduce the cost and form factor of coherent transceivers, full integration of photonic devices including lasers, modulators, amplifiers, photodetectors, and other components is necessary. However, as fabricating optical isolators on chip remains extremely challenging, optical feedback, which can degrade the coherence of semiconductor lasers, becomes the main obstacle, thwarting large-scale photonic integration. An appealing solution to such a problem is to use semiconductor lasers with intrinsic insensitivity to optical feedback as the integrated light sources. The heterogenous Si/III-V lasers, with their built-in high-Q resonators, are expected to possess a robustness to optical feedback which exceeds by several orders of magnitude compared to commercial III-V distributed feedback (DFB) lasers, which will be validated here. We present data showing that the heterogeneous Si/III-V lasers can preserve their phase coherence under much larger optical feedback and therefore function without severe degradation in isolator-free coherent optical communication systems.

Sub-Nyquist radar systems operate at lower sampling rates compared to the Nyquist rate and hence reduce the hardware cost and complexity. Sub-Nyquist systems uses the knowledge of the transmit pulse and the receive signal model to estimate the targets from lowrate samples. However, in practice, the pulse shape is often distorted and unknown at the receiver. Recently, a multiple-receiver based sub-Nyquist radar was proposed that estimates the targets without knowledge of the pulse shape. In this demo, we build a hardware prototype to demonstrate the proposed sub-Nyquist radar. We show that while operating at 10 times below the Nyquist rate the proposed two-receiver system with unknown pulse has comparable performance to a single-receiver sub-Nyquist system with a known pulse.

Antibodies are widely used in therapeutic, diagnostic, and research applications, and antibody derivatives such as F(ab')2 fragments are used when only a particular antibody region is required. F(ab')2 can be produced through antibody engineering, but some applications require F(ab')2 produced from an original formulated antibody or directly from a polyclonal antibody pool. The cysteine protease immunoglobulin-degrading enzyme (IdeS) from Streptococcus pyogenes digests immunoglobulin G (IgG) specifically and efficiently to produce F(ab')2 . Here we detail the production and purification of recombinant IdeS; its utilization to digest monoclonal or polyclonal antibodies to F(ab')2 fragments; and F(ab')2 purification through consecutive affinity chromatography steps. The resultant F(ab')2 exhibit high purity, retain antigen-binding functionality, and are readily utilizable in various downstream applications. © 2020 by John Wiley & Sons, Inc. Basic Protocol: Production and purification of F(ab')2 fragments from monoclonal and polyclonal antibodies using IdeS Alternate Protocol: Purification of polyclonal antigen-specific F(ab')2 fragments from human serum or secretions Support Protocol: Production and purification of IdeS.

A new strand of writing in political philosophy deals with the linkage – rather than the tension – between politics of recognition and politics of redistribution. This scholarship usually deals wit...

We present a fast randomized algorithm that computes a low rank LU decomposition. Our algorithm uses random projections type techniques to efficiently compute a low rank approximation of large matrices. The randomized LU algorithm can be parallelized and further accelerated by using sparse random matrices in its projection step. Several different error bounds are proven for the algorithm approximations. To prove these bounds, recent results from random matrix theory related to subgaussian matrices are used. As an application, we also show how the algorithm can be utilized to solve problems such as the rank-deficient least squares problem. Numerical examples, which illustrate the performance of the algorithm and compare it to other decomposition methods, are presented.

Shear-driven flows over superhydrophobic surfaces formed of closely spaced circular bubbles are characterized by giant longitudinal slip lengths, viz., large compared with the periodicity (Schnitzer, Phys Rev Fluids 1(5):052101, 2016). This hints towards a strong superhydrophobic effect in the concomitant scenario of pressure-driven flow between two such surfaces, particularly for non-wide channels where bubble-to-bubble pitch and bubble radius are commensurate with channel width. We show here that such pressure-driven flows can be analyzed asymptotically and in closed form based on the smallness of the gaps separating the bubbles relative to the channel width (and bubble radius). We find that the flow adopts an unconventional plug profile away from the inter-bubble gaps, with the uniform velocity being asymptotically larger than the corresponding Poiseuille scale. For a given solid fraction and channel width, the net volumetric flux is maximized when the length of each semi-circular bubble-liquid interface is equal to the channel width. The plug flow identified herein cannot be obtained via a naive implementation of a Navier condition, which is indeed inapplicable for non-wide channels.

We demonstrate a narrow-linewidth heterogeneously integrated Si/III–V laser, where the current confinement in the III–V structure is obtained by oxide isolation rather than by the prevailing ion-implantation technique. This method provides effective electrical isolation as well as III–V surface passivation, and a pathway for high-efficiency diode injection laser performance. This method also offers increased compatibility with potentially high-temperature annealing processes. The lasers shown here possess a threshold current of as low as 60 mA and a single-facet output power of more than 3 mW at 20 °C. A linewidth of 28 kHz at 1574.8 nm is obtained at a current of 200 mA ( $I = 3.3 \times I_{\mathrm{ th}}$ ). Single-mode operation is achieved with a side-mode suppression ratio larger than 55 dB.

Here we present a new paradigm of free-electron-bound-electron resonant interaction. This concept is based on a recent demonstration of the optical frequency modulation of the free-electron quantum electron wave function (QEW) by an ultrafast laser beam. We assert that pulses of such QEWs correlated in their modulation phase, interact resonantly with two-level systems, inducing resonant quantum transitions when the transition energy ΔE=ℏω_{21} matches a harmonic of the modulation frequency ω_{21}=nω_{b}. Employing this scheme for resonant cathodoluminescence and resonant EELS combines the atomic level spatial resolution of electron microscopy with the high spectral resolution of lasers.

Improper suturing may cause an inadequate wound healing process and wound dehiscence as well as infection and even graft rejection in case of corneal transplantation. Hence, training surgeons in correct suturing procedures and objectively assessing their surgical skills is desirable. Two complementary methods for assessment of suturing skills in two medical fields (general surgery and ocular microsurgery) were demonstrated. Suturing quality is assessed by computer vision software. Evaluation of stitching flow of operation is based on measuring strain induced in an optical fiber that is placed in proximity to the wound and parallel thereto and is pressed and passed by wound stitches. Our software generated a score for suturing outcome in both general surgery and ocular microsurgery when the stitching was done on a patch. Every trainee received a score in the range 0–100 that describes his/her performance. Strain values were recognized when using a patch in general surgery and a rubber patch in ocular microsurgery, but were less distinct in (disqualified) human cornea. We proved a concept of an objective scoring method (based on various image processing algorithms) for assessment of suturing performance. It was also shown that fiber optic strain sensors are sensitive to the flow of stitching operation on a patch but are less sensitive to the flow of stitching operation on a human cornea. By combining these two methods, we can comprehensively evaluate the suturing performance objectively.

Background: Recent evidence suggests that pregnant women might be at higher risk of severe disease associated with the emerging pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), while exposed fetuses/newborns could suffer from preterm birth, growth restriction and neonatal infections. The magnitude of this increased risk and specific risk factors for severity remains unclear. Methods: We performed a case control study comparing pregnant women with severe coronavirus disease 19 (case) to pregnant women with a milder form (controls) enrolled in COVI-Preg international registry cohort between from March 24 to July 26, 2020. Risk factors for severity, obstetrical, fetal and neonatal outcomes were assessed. Findings: A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented a severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of cesarean sections [70.7% (n=53/75)], preterm deliveries [62.7% (n= 32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n=31/75)]. Interpretation: Pregnant women, particularly those with associated comorbidities, seem to be at higher risk of severe complications of SARS-CoV-2 infection. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease; complications include cesarean sections, prematurity and neonatal admission to the intensive care unit. Funding Statement: None. Declaration of Interests: The authors declare that they have no conflicts of interest. Ethics Approval Statement: The study was approved by both the Swiss Ethical Board (CER-VD- 2020-00548) and the local ethics boards at each participating center.

Dual-function radar-communications (DFRC) systems implement radar and communication functionalities on a single platform. Jointly designing these subsystems can lead to substantial gains in performance as well as size, cost, and power consumption. In this paper, we propose a DFRC system, which utilizes generalized spatial modulation (GSM) to realize coexisting radar and communications waveforms. Our proposed GSM-based scheme, referred to as spatial modulation based communication-radar (SpaCoR) system, allocates antenna elements among the subsystems based on the transmitted message, thus achieving increased communication rates by embedding additional data bits in the antenna selection. We formulate the resulting signal models, and present a dedicated radar processing scheme. To evaluate the radar performance, we characterize the statistical properties of the transmit beam pattern. Then, we present a hardware prototype of the proposed DFRC system, demonstrating the feasibility of the scheme. Our results show that the proposed GSM system achieves improved communication performance compared to techniques utilizing fixed allocations operating at the same data rate. For the radar subsystem, our experiments show that the spatial agility induced by the GSM transmission improves the angular resolution and reduces the sidelobe level in the transmit beam pattern compared to using fixed antenna allocations., Comment: 14pages

Introduction Proximal humerus nails (PHN) are commonly used for the treatment of simple proximal humerus fractures, and have a reported malunion rate of about 10%. The surgeons who used PHN in one medical institution have noticed a high rate of fracture re-displacement in the early post-operative period. This study's aim is to evaluate the rate of secondary displacement and malunion of patients treated for two part proximal humerus fractures with an angle-stable PHN (MultiLoc), and to assess possible risk factors for this secondary displacement. Methods A retrospective study comprised of 25 consecutive patients with 2 part surgical neck or metaphysis displaced proximal humerus fracture, treated with PHN between the years 2014–2017. Results assessed included radiographic measures (neck-shaft angle) and clinical data: range of motion (ROM) and functional scores (Constant, DASH, SSV). A univariate regression analysis was used to assess possible risk factors for secondary displacement. Results Mean age was 66.6 (range 17–93), and mean follow up was 20 months (range 6–40). Mean neck shaft angle (NSA) changed from 139.1° post operatively to 122.6° at last follow up, with 6 patients (24%) having a NSA change larger than 20°. Two patients (8%) ended up with NSA less than 90°, defined as malunion. The deltoid tuberosity index was found to correlate with the degree of displacement (−0.41, p = 0.04). Conclusions PHN for simple displaced proximal humerus fractures was associated with fair clinical results but an unacceptable rate secondary displacement. The deltoid tuberosity index was found to correlate with the degree of this secondary displacement.

Objective To evaluate maternal and perinatal outcomes after induction of labour versus expectant management in pregnant women with gestational diabetes at term. Design Multicentre open-label randomised controlled trial. Setting Eight teaching hospitals in Italy, Slovenia, and Israel. Sample Singleton pregnancy, diagnosed with gestational diabetes by the International Association of Diabetes and Pregnancy Study Groups criteria (IADPSGC), between 38+0 and 39+0 weeks of gestation, without other maternal or fetal conditions. Methods Patients were randomly assigned to induction of labour or expectant management and intensive follow-up. Data were analysed by ‘intention to treat’. Main outcome measures The primary outcome was incidence of caesarean section. Secondary outcomes were maternal and perinatal mortality and morbidity. Results A total of 425 women were randomised to the study groups. The incidence of caesarean section was 12.6% in the induction group versus 11.7% in the expectant group. No difference was found between the two groups (relative risk, RR 1.06; 95% confidence interval, 95% CI 0.64–1.77; P = 0.81). The incidence of non-spontaneous delivery, either by caesarean section or by operative vaginal delivery, was 21.0 and 22.3%, respectively (RR 0.94; 95% CI 0.66–1.36; P = 0.76). Neither maternal nor fetal deaths occurred. The few cases of shoulder dystocia were solved without any significant birth trauma. Conclusions In women with gestational diabetes, without other maternal or fetal conditions, no difference was detected in birth outcomes regardless of the approach used (i.e. active versus expectant management). Although the study was underpowered, the magnitude of the between-group difference was very small and without clinical relevance. Tweetable abstract Immediate delivery or expectant management in gestational diabetes at term?

We demonstrate that high-coherence Si/III-V hybrid lasers are much more robust than conventional III-V DFB lasers against both coherent and incoherent optical feedback by examining the frequency noise power spectral density of the lasers.

We have demonstrated the use of a hybrid Si/III-V semiconductor laser to carry 20-Gbaud 16- and 64-QAM data signals over an 80-km fiber. The high coherence of the laser enables below FEC threshold performance after transmission.

We experimentally demonstrate the use of a high-coherence hybrid silicon (Si)/III–V semiconductor laser as the light source for a transmitter generating 20 Gbaud 16- and 64- quadrature amplitude modulated (QAM) data signals over an 80 km single-mode fiber (SMF) link. The hybrid Si/III–V laser has a measured Schawlow–Townes linewidth of ∼ 10 k H z , which is achieved by storing modal optical energy in low-loss Si, rather than the relatively lossy III–V materials. We measure a received bit error rate (BER) of 4.1 × 10 − 3 when transmitting the 64-QAM data over an 80 km SMF using the hybrid Si/III–V laser. Furthermore, we measure a BER of < 1 × 10 − 4 with the Viterbi–Viterbi digital carrier phase recovery method when transmitting the 16-QAM data over an 80 km SMF using the hybrid Si/III–V laser. This performance is achieved at power penalties lower than those obtained with an exemplary distributed feedback laser and slightly higher than those with an exemplary narrow-linewidth external cavity laser.

Significance The semiconductor laser, arguably the most versatile member of the family of lasers, has become a technological staple of a massively interconnected, data-driven world, with its spectral purity (i.e., temporal coherence) an increasingly important figure of merit. The present work describes a conceptually fundamental “recipe” for the enhancement of coherence, predicated on direct control of the coherence-limiting process itself, the field–matter interaction. As such, it is inherently adaptable and technologically scalable. As photonic materials and fabrication techniques continue to improve, the described approach has the potential of serving as a roadmap for major and sustained improvements in coherence. With experimentally demonstrated coherence limited at 1 kHz in this work, we envision “deep” sub-kilohertz-level coherence to be soon within reach., Few laser systems allow access to the light–emitter interaction as versatile and direct as that afforded by semiconductor lasers. Such a level of access can be exploited for the control of the coherence and dynamic properties of the laser. Here, we demonstrate, theoretically and experimentally, the reduction of the quantum phase noise of a semiconductor laser through the direct control of the spontaneous emission into the laser mode, exercised via the precise and deterministic manipulation of the optical mode’s spatial field distribution. Central to the approach is the recognition of the intimate interplay between spontaneous emission and optical loss. A method of leveraging and “walking” this fine balance to its limit is described. As a result, some two orders of magnitude reduction in quantum noise over the state of the art in semiconductor lasers, corresponding to a minimum linewidth of 1 kHz, is demonstrated. Further implications, including an additional order-of-magnitude enhancement in effective coherence by way of control of the relaxation oscillation resonance frequency and enhancement of the intrinsic immunity to optical feedback, highlight the potential of the proposed concept for next-generation, integrated coherent systems.

We report for the first time, to the best of our knowledge, an all-fiber Raman graded-index (GRIN) fiber laser pumped by a fiber laser. This configuration points to potential future power and brightness increases. Continuous-wave power of 135 W with an M2 value of 2.5 was obtained at a wavelength of 1081 nm with an optical-to-optical efficiency of 68%. A commercial GRIN core fiber acts as the Raman fiber in a power oscillator configuration that includes fiber Bragg gratings (FBGs) written onto the GRIN fiber. The efficiency and brightness demonstrated here are, to the best of our knowledge, the highest reported in any Raman GRIN fiber laser. A brightness enhancement of the pump beam by a factor of 5.6 is attained due to the transverse profiles of Raman gain and FBG reflection in the GRIN fiber.

We report a strictly all-fiber clad pumped Raman fiber laser with a CW power of 250 W. To the best of our knowledge, this is the highest power Raman fiber laser demonstrated in any configuration allowing brightness enhancement. In addition, this is the first report of a Raman clad pumped all-fiber laser. The brightness of the pump source was enhanced by a factor of ∼3.8. This result was achieved by the design of a novel triple-clad fiber, with tight pump power inner confining clad that both maximized the Raman gain and inhibited the second Stokes radiation. We discuss power-increase effects on the beam quality, efficiency, and brightness enhancement.

We report a simple robust and broadly spectral-adjustable source generating near fully compressed 1053 nm 62 fs pulses directly out of a highly-nonlinear photonic crystal fiber. A dispersion-nonlinearity balance of 800 nm Ti:Sa 20 fs pulses was obtained initially by negative pre-chirping and then launching the pulses into the fibers' normal dispersion regime. Following a self-phase modulation spectral broadening, some energy that leaked below the zero dispersion point formed a soliton whose central wavelength could be tuned by Self-Frequency-Raman-Shift effect. Contrary to a common approach of power, or, fiber-length control over the shift, here we continuously varied the state of polarization, exploiting the Raman and Kerr nonlinearities responsivity for state of polarization. We obtained soliton pulses with central wavelength tuned over 150 nm, spanning from well below 1000 to over 1150 nm, of which we could select stable pulses around the 1 μm vicinity. With linewidth of > 20 nm FWHM Gaussian-like temporal-shape pulses with ∼ 62 fs duration and near flat phase structure we confirmed high quality pulse source. We believe such scheme can be used for high energy or high power glass lasers systems, such as Nd or Yb ion-doped amplifiers and systems.

CRISPR/Cas9 has become a powerful tool for genome editing in zebrafish that permits the rapid generation of loss of function mutations and the knock-in of specific alleles using DNA templates and homology directed repair (HDR). We examined the efficiency of synthetic, chemically modified gRNAs and demonstrate induction of indels and large genomic deletions in combination with recombinant Cas9 protein. We developed an in vivo genetic assay to measure HDR efficiency and we utilized this assay to test the effect of altering template design on HDR. Utilizing synthetic gRNAs and linear dsDNA templates, we successfully performed knock-in of fluorophores at multiple genomic loci and demonstrate transmission through the germline at high efficiency. We demonstrate that synthetic HDR templates can be used to knock-in bacterial nitroreductase (ntr) to facilitate lineage ablation of specific cell types. Collectively, our data demonstrate the utility of combining synthetic gRNAs and dsDNA templates to perform homology directed repair and genome editing in vivo.

The article discusses the choice between the current arm's length based transfer pricing regime and a formula-based transfer pricing regime. It argues that a reform of our transfer pricing rules is imminent, even if it is not part of a comprehensive reform of the international tax regime (a necessary yet a more complex goal to meet). The article demonstrates that many of the objections to a formula-based transfer pricing reform may be valid in the context of the more comprehensive reform of the business income tax rules, but not, or to a lesser extent, in the context of the narrower transfer pricing reform. It concludes therefore that much of the objection to formulary apportionment becomes irrelevant in a narrower scoped reform, and that the ground is ripe for it.

Most vaccines confer protection via the elicitation of serum antibodies, yet more than 100 y after the discovery of antibodies, the molecular composition of the human serum antibody repertoire to an antigen remains unknown. Using high-resolution liquid chromatography tandem MS proteomic analyses of serum antibodies coupled with next-generation sequencing of the V gene repertoire in peripheral B cells, we have delineated the human serum IgG and B-cell receptor repertoires following tetanus toxoid (TT) booster vaccination. We show that the TT(+) serum IgG repertoire comprises ∼100 antibody clonotypes, with three clonotypes accounting for40% of the response. All 13 recombinant IgGs examined bound to vaccine antigen with Kd ∼ 10(-8)-10(-10) M. Five of 13 IgGs recognized the same linear epitope on TT, occluding the binding site used by the toxin for cell entry, suggesting a possible explanation for the mechanism of protection conferred by the vaccine. Importantly, only a small fraction (5%) of peripheral blood plasmablast clonotypes (CD3(-)CD14(-)CD19(+)CD27(++)CD38(++)CD20(-)TT(+)) at the peak of the response (day 7), and an even smaller fraction of memory B cells, were found to encode antibodies that could be detected in the serological memory response 9 mo postvaccination. This suggests that only a small fraction of responding peripheral B cells give rise to the bone marrow long-lived plasma cells responsible for the production of biologically relevant amounts of vaccine-specific antibodies (near or above the Kd). Collectively, our results reveal the nature and dynamics of the serological response to vaccination with direct implications for vaccine design and evaluation.

Utilizing the surface plasmon resonance (SPR) effect of gold nanoparticles (GNPs) enables their use as contrast agents in a variety of biomedical applications for diagnostics and treatment. These applications use both the very strong scattering and absorption properties of the GNPs due to their SPR effects. Most imaging methods use the light-scattering properties of the GNPs. However, the illumination source is in the same wavelength of the GNPs’ scattering wavelength, leading to background noise caused by light scattering from the tissue. In this paper we present a method to improve border detection of regions enriched with GNPs aiming for the real-time application of complete tumor resection by utilizing the absorption of specially targeted GNPs using photothermal imaging. Phantoms containing different concentrations of GNPs were irradiated with a continuous-wave laser and measured with a thermal imaging camera which detected the temperature field of the irradiated phantoms. By modulating the laser illumination, and use of a simple post processing, the border location was identified at an accuracy of better than 0.5 mm even when the surrounding area got heated. This work is a continuation of our previous research.

In a high power fiber amplifier, a frequency-chirped seed interrupts the coherent interaction between the laser and Stokes waves, raising the threshold for stimulated Brillouin scattering (SBS). Moving the external mirror of a vertical cavity surface-emitting diode laser 0.2 μm in 10 μs can yield a frequency chirp of 5×1017 Hz/s5×1017 Hz/s at a nearly constant output power. Opto-electronic feedback loops can linearize the chirp, and stabilize the output power. The linear variation of phase with time allows multiple amplifiers to be coherently combined using a frequency shifter to compensate for static and dynamic path length differences. The seed bandwidth, as seen by the counter-propagating SBS, also increases linearly with fiber length, resulting in a nearly-length-independent SBS threshold. Experimental results at the 1.6 kW level with a 19 m delivery fiber are presented. A numerical simulation is also presented.

We observe a relaxation resonance frequency of hundreds of MHz in high-coherence Si/III-V lasers, up to 5× less than commercial III-V lasers. This results in very noise frequency noise PSD of 720 Hz2/Hz above the relaxation resonance frequency due to the suppression of linewidth enhancement factor.

Air traffic control radar, military air traffic surveillance radars, meteorological radars and mobile wireless communication operate in the S-band frequency range. Test and measurement of spectrum sharing methods and their co-existence is absolutely essential, as performance degradation of mobile devices, networks ans S-Band radars has been proven. This paper addresses potential issues, discusses approaches to testing and measuring LTE and S-band radar co-existence.

Adolescent heroin and other opioid abuse is a significant public health concern. Prescription opioid abuse among youth has been estimated to have increased over 500% in the past decade, making prescription opioids the second most commonly abused illicit drug among adolescents in the U.S. The annual prevalence rates (past year use for 2009) for OxyContin (a controlled-release form of oxycodone hydrochloride that promotes rapid euphoria when crushed before consumption) is 2.0 %, 5.1 % and 4.9 % in 8th, 10th, and 12th grades, respectively while annual prevalence rates (past year use for 2008) for Vicodin (hydrocodone/acetaminophen) is 2.5 %, 8.1 %, and 9.7 % across the same grades. Data from the Monitoring the Future Study (MTFS, 2009) indicate that the annual prevalence of heroin use has leveled off in recent years and is below 1% across 8th, 10th and 12th grades (0.5 %, 0.6 %, and 0.3 %, respectively, for past year use for 2009). Significantly, recreational opioid use has been suggested to be a new route to heroin abuse and dependence (Siegal et al., 2003). Consistent with the increasing prevalence of opioid abuse among adolescents, treatment admissions for substance use disorders (SUDs) among youth who identified opioids as their primary drugs of abuse increased by 35% (82% for prescription opioids, 4.9% for heroin) from 1997 to 2007, according to the most recently published estimates (Substance Abuse and Mental Health Services Administration (SAMHSA) Office of Applied Studies (OAS), 2009). Despite the mounting evidence supporting the prevalence of the problem of adolescent opioid use as well as the treatment needs of these adolescents, limited research has been conducted with this population (Subramaniam et al., 2009). The few studies that have described the characteristics of treatment-seeking adolescent opioid users (Clemmey et al., 2004; Crome et al., 1998; Gordon, 2002; Gordon et al., 2004; Hopfer et al, 2000; Marsch et al., 2005; Perry & Duroy, 2004; and Pugatch et al, 2001) have typically focused on adolescent heroin users and have characterized them as typically white and male. This group has been shown to typically start experimenting with substances as young as 10 years; report daily use of heroin; report administering heroin intravenously; and experience a number of legal and/or psychiatric problems. Even fewer studies have characterized adolescents who use prescription opioids (Sung et al, 2005; McCabe et al, 2005), highlighting that similar to adolescent heroin users, this group is generally white. Although the scientific literature on the treatment of adults who are opioid dependent is extensive, only two published randomized, controlled trials to date have focused on the systematic evaluation of treatments for youth with opioid use disorders. One such study (Woody et al., 2008) evaluated the use of buprenorphine combined with naloxone (Suboxone®), among an adolescent and young adult population (15–21 yrs). Overall, patients in the 14-day outpatient Suboxone detox group had a higher proportion of opioid-positive urine test results, compared with those in 12 weeks of Suboxone treatment. By week 12, 20.5% of detox patients remained in treatment vs. 70% of participants receiving the 12-week treatment. Further, almost all of the other secondary outcomes, including reduced injection drug use and lower participation rates in non-study addiction treatment, favored the longer course of buprenorphine. The second such trial is, to our knowledge, the only published, randomized clinical trial to date that has examined treatment outcomes specifically among opioid-dependent adolescents (Marsch et al. 2005). Adolescent participants (ages 13–18 eligible) were randomly assigned to a 28-day detox with buprenorphine or clonidine. In addition to the medication, all participants received intensive behavioral therapy drawing on the Community Reinforcement Approach (CRA; Meyers and Miller, 2001), and vouchers (positive rewards) for opioid-negative urines, attendance, and weekly assessments. Results demonstrated that overall, buprenorphine was more efficacious than clonidine in treating this population of adolescents dependent on opioids when combined with intensive behavioral therapy. In particular, retention was better (72% vs. 36%) and there were more opioid-negative urines (64% vs. 32%) among those who received buprenorphine relative to those who received clonidine. Numerous treatment studies conducted with adult substance-using populations have demonstrated that individuals’ psychosocial functioning often improves along with their substance use during treatment (Brook & Whitehead, 1980; De Leon, 1984; 1989), although it is important to note that some psychopathological symptoms pre-date substance abuse, while others are the result of pharmacological effects of the substances. To our knowledge, no systematic research to date has specifically examined the extent to which opioid-dependent youths’ psychopathology (emotional and behavioral problems) may be impacted from substance abuse treatment. Such an investigation is warranted due to the well-established association of psychopathology and substance use among adolescents with opioid use disorders (Subramaniam et al., 2009). Additionally, understanding the extent to which emotional and behavioral problems improve among youth during treatment for opioid dependence is important for better understanding how their quality of life may be improved during treatment. The Youth Self-Report (YSR; Achenbach and Rescorla, 2001) is a commonly used measure of emotional and behavioral problems among youth; and despite wide use in over twenty countries, this instrument has been infrequently used to characterize youth who are seeking treatment for substance abuse. The YSR assesses three broad areas: competence and adaptive scales, empirically based syndrome scales that load onto superordinate grouping scales (internalizing, externalizing, and total problems) and DSM-oriented scales (which were more recently added to relate syndrome scales to DSM criteria). A search of a variety of scientific databases as well as the Achenbach System of Empirically Based Assessment (ASEBA) Bibliographic database (www.asebabib.org) revealed only a handful of studies utilizing the measure with adolescent substance abuse treatment seeking samples. To our knowledge, only three of these studies have used the YSR to prospectively examine treatment outcomes among substance-using adolescents (Waldron et al., 2007; Kamon, et al., 2005; Rivers et al., 2001). No statistically significant reductions in internalizing or externalizing scales scores on the YSR were observed among youth in the first two studies. However, Rivers et al. found that among adolescents participating in an 8-week hospital-based, adolescent substance abuse program, across all 8 YSR scales used, female participants showed statistically significant improvements in their scale scores. Male participants made modest changes on only the Somatic Complaints scale. The present study used the YSR to examine changes in behavioral and emotional problems among opioid-dependent adolescents enrolled in a randomized, controlled trial designed to evaluate the efficacy of combined behavioral-pharmacological treatments for opioid-dependent adolescents (Marsch et al., 2005). To our knowledge, the present study is the first to use the YSR as an outcome measure to assess changes in psychopathology during behavioral-pharmacological treatment for opioid-dependent adolescents.