Cross-cultural representations of conjoined twins.

Conjoined twinning is a rare birth defect estimated to occur in about 1 in 50,000 to 100,000 births. The mechanism of conjoined twinning is not proven. Different forms of conjoined twinning are observed with the thoracopagus form being the most common. The rate of conjoined twinning is similar across all major populations. A dramatic malformation of this type would be an extraordinary occurrence leading people to reflect on the spiritual or supernatural nature of such an event. Therefore, it is not surprising that artifacts that seem to depict different forms of conjoined twins are seen across diverse cultures. In this article, we present a survey of these cultural artifacts including anatomic classification based on external anatomy and an exploration of the cultural and spiritual contexts associated with the artifacts. A key finding is that the most common form of conjoined twinning in the artifacts is parapagus (both dicephalus and diprosopus) in contrast to thoracopagus, the most common form in epidemiologic studies. Potential reasons for this difference are discussed. Evidence is presented to support the speculation that these objects represent artistic impressions of actual conjoined twinning events.

Impact of nonlinearity including bleaching in MUTC photodetectors on RF-modulated electro-optic frequency combs.

We use the drift-diffusion equations to calculate the responsivity of a modified uni-traveling carrier (MUTC) photodetector (PD) with a frequency comb input that is generated by a series of short optical pulses. We first use experimental results for the responsivity of the MUTC PD to obtain an empirical model of bleaching in pulsed mode. We incorporate our empirical bleaching model into a drift-diffusion model to calculate the impact of nonlinearity in an MUTC PD on RF-modulated electro-optic frequency combs. We quantify the nonlinearity using the second- and third-order intermodulation distortion powers (IMD2 and IMD3), from which we calculate the second- and third-order output intercept points (OIP2 and OIP3). In contrast to a continuous wave (CW) input for which there is a single IMD2 and IMD3 and hence a single OIP2 and OIP3, each comb line n has its own IMD2n, IMD3n, OIP2n, and OIP3n associated with it. We determine the IMD2n, IMD3n, OIP2n, and OIP3n, and we compare the results with and without bleaching. We find that the impact of bleaching is complex and, somewhat surprisingly, not always detrimental. The principal effect of bleaching is to lower the responsivity, which decreases the nonlinearity due to space charge. While bleaching always reduces the OIP2n and OIP3n, we find that bleaching leads to a decreased distortion-to-signal ratio for large n.

Comparison of the impact of nonlinearity in a p-i-n and an MUTC photodetector on electro-optic frequency combs.

We calculate the impact of nonlinearity in both a p-i-n photodetector (PD) and a modified uni-traveling carrier (MUTC) PD on an RF-modulated frequency comb generated using 100-fs optical pulses with a 50-MHz repetition rate. We take into account bleaching (nonlinear saturation) that is due to the high peak-to-average-power ratio and contributes to the device nonlinearity. Nonlinear impairment of an RF-modulated continuous wave is typically characterized by the second- and third-order intermodulation distortion products (IMD2 and IMD3). In contrast, an RF-modulated frequency comb must be characterized by a distinct IMD2n and IMD3n for each comb line n. We calculate IMD2n and IMD3n in both p-i-n and MUTC PDs and compare the results. We also calculate the ratio of the IMD2n power and the IMD3n power to the fundamental power Sin in both p-i-n and MUTC PDs. We find that nonlinear distortion has a greater impact at high frequencies in the MUTC PD than in the p-i-n PD.

Calculation of the impulse response and phase noise of a high-current photodetector using the drift-diffusion equations.

We describe a procedure to calculate the impulse response and phase noise of high-current photodetectors using the drift-diffusion equations while avoiding computationally expensive Monte Carlo simulations. We apply this procedure to a modified uni-traveling-carrier (MUTC) photodetector. In our approach, we first use the full drift-diffusion equations to calculate the steady-state photodetector parameters. We then perturb the generation rate as a function of time to calculate the impulse response. We next calculate the fundamental shot noise limit and cut-off frequency of the device. We find the contributions of the electron, hole, and displacement currents. We calculate the phase noise of an MUTC photodetector. We find good agreement with experimental and Monte Carlo simulation results. We show that phase noise is minimized by having an impulse response with a tail that is as small as possible. Since, our approach is much faster computationally than Monte Carlo simulations, we are able to carry out a broad parameter study to optimize the device performance. We propose a new optimized structure with less phase noise and reduced nonlinearity.

Frequency dependent harmonic powers in a modified uni-traveling carrier photodetector.

We use a drift-diffusion model to study frequency dependent harmonic powers in a modified uni-traveling carrier (MUTC) phododetector. The model includes external loading, incomplete ionization, the Franz-Keldysh effect, and history-dependent impact ionization. In three-tone measurements, the bias voltage at which a null occurs (bias null) in the second-order intermodulation distortion (IMD2) is different for the sum frequency and difference frequency. We obtained agreement with the experimental results. The bias null that appears in the IMD2 is due to the Franz-Keldysh effect. The bias voltage at which the bias null is located depends on the electric field in the intrinsic region, and the difference in the location of the bias null for the sum frequency and difference frequency is due to the displacement current in the intrinsic region. When the frequency is large, the displacement current is large and has a large effect on the harmonic powers. We also found that the bias null depends on the recombination rate in the p-absorption region because the electric field decreases in the intrinsic region when the recombination rate in the p-region decreases.

Impact of the Coulomb interaction on the Franz-Keldysh effect in high-current photodetectors.

The Franz-Keldysh effect has been recognized as the largest contributor to oscillations in the responsivity of high-current photodetectors as a function of the applied bias or the incident light wavelength and to device nonlinearity. Prior work only considered the effect of the electric field without considering the Coulomb interaction. We show that it is not possible to obtain agreement with experiments at all optical wavelengths without including this effect in the effective mass equation. We find the maxima and minima in the absorption of the applied electric field shift when the Coulomb interaction is included. We then use the calculated absorption with the drift-diffusion equations to calculate the responsivity in a partially depleted absorber (PDA) photodetector, and we obtain excellent agreement with experiments at all biases and optical wavelengths.

Simulation of a partially depleted absorber (PDA) photodetector.

We use a 2D drift-diffusion model to study the nonlinear response of a partially depleted absorber (PDA) phododetector. The model includes external loading, incomplete ionization, the Franz-Keldysh effect, and history-dependent impact ionization. It also takes into account heat flow in the device. With all these effects included, we obtain excellent agreement with experiments for the responsivity and for the harmonic power at different modulation frequencies. The role of these different physical effects is elucidated, and we find that both the Franz-Keldysh effect and the load resistance play a key role in generating higher harmonic power at larger reverse biases. Increasing the size of the p-region absorption layers reduces the impact of the Franz-Keldysh effect. Decreasing the effective load resistance also decreases the higher harmonic powers. We also show that the model can suggest design changes that will improve device performance.

Analysis of magnitude and relative phase of photodiode IMD2 using amplitude matched MZM-distortion cancellation technique.

We present a detailed look at using Mach-Zehnder modulator generated distortion for identifying the magnitude and relative sign of photodiode generated second order intermodulation distortion (IMD2). Previous discussions introduced the concept for characterizing a test device. Analysis is expanded to IMD2 as a function of voltage, photocurrent and frequency.

Suppression of even-order photodiode distortions via predistortion linearization with a bias-shifted Mach-Zehnder modulator.

A new technique to cancel photodiode-induced even-order distortion in microwave photonic links is demonstrated. A single Mach-Zehnder modulator, biased slightly away from the quadrature point, is shown to suppress photodiode second-order intermodulation distortion in excess of 40 dB without affecting the fundamental power. The technique is theoretically described with supporting experimental results.

Cancellation of photodiode-induced second harmonic distortion using single side band modulation from a dual parallel Mach-Zehnder.

We have theoretically and experimentally investigated using a dual parallel Mach-Zehnder modulator (DP-MZM) in an RF photonic link to cancel the second harmonic distortion due to the photodiode. Biasing the DP-MZM for single sideband modulation, the second harmonic generated by the DP-MZM can be set out of phase with the second harmonic generated at the photodiode. We measure the output intercept point of the second harmonic distortion of the link to be 55.3 dBm, which is an improvement of over 32 dB as compared to only the photodiode.

Comparison of photodiode nonlinearity measurement systems.

Photodiode nonlinearity measurements using one-, two- and three-tone measurement systems are compared with each other, to investigate the comparison accuracy between setups. The mathematical relationship between each setup is analyzed, and data on multiple devices are compared to find under which conditions the measurements are comparable. It is shown that the three measurement systems can be used interchangeably only when the distortion adheres to the expected mathematical slopes.

Measurement of intermodulation distortion in high-linearity photodiodes.

Accurately characterizing third order intermodulation distortion (IMD3) in high-linearity photodiodes is challenging. Two measurement techniques are evaluated-a standard two-tone measurement and a more complicated three-tone measurement technique to measure IMD3. A model of the measurement system is developed and used to analyze the limitations of the two techniques in determining the distortion of highly linear photodiodes. Experimental validation is provided by comparing the simulation trends with IMD3 results measured on two types of waveguide photodiodes: 1) an InP based uni-traveling-carrier (UTC) photodiode and 2) a Ge n-i-p waveguide photodetector on Silicon-on-Insulator (SOI) substrate.

The changing face of febrile neutropenia-from monotherapy to moulds to mucositis. Why monotherapy?

This is an account of the history of the early days of monotherapy of infections in neutropenic patients with haematological malignancies. A chance encounter with Ben de Pauw led to his introduction to clinical drug development research, introduced him to Peter Donnelly who was studying ceftazidime at the Hammersmith Hospital in London and led to a series of collaborative studies at the start of a distinguished research career. This paper is dedicated to Ben de Pauw and also to the memory of my mentor, Roy Foord, who had the vision to go against his initial cautious instinct and allow me to convince him of the merits of these studies when combinations including aminoglycosides were standard. These initial studies also contributed to the concept of initial empirical monotherapy with re-appraisal at 48-72 h.

Investigation of electrooptic modulator disruption by microwave-induced transients.

This paper presents a detailed investigation of the physical mechanisms underlying the disruption of a lithium niobate electrooptic modulator by RF pulses. It is shown that short-term modulator disruption is a direct consequence of resistive heating within the metal conductor of the coplanar waveguide electrode, which leads to a thermo-optic optical phase shift in the waveguides of the modulator. Resistive heating is also shown to contribute to permanent modulator damage at higher RF power. These results indicate that short-term RF disruption, and possibly RF damage, can be mitigated through improved thermal management. They also predict that short-term photonic link disruption can be reduced, if not eliminated, by use of a phase modulated photonic link.

Even-order harmonic cancellation for off-quadrature biased Mach-Zehnder modulator with improved RF metrics using dual wavelength inputs and dual outputs.

We present a technique using a dual-output Mach-Zehnder modulator (MZM) with two wavelength inputs, one operating at low-bias and the other operating at high-bias, in order to cancel unwanted even-order harmonics in analog optical links. By using a dual-output MZM, this technique allows for two suppressed optical carriers to be transmitted to the receiver. Combined with optical amplification and balanced differential detection, the RF power of the fundamental is increased by 2 dB while the even-order harmonic is reduced by 47 dB, simultaneously. The RF noise figure and third-order spurious-free dynamic range (SFDR(3)) are improved by 5.4 dB and 3.6 dB, respectively. Using a wavelength sensitive, low V(pi) MZM allows the two wavelengths to be within 5.5 nm of each other for a frequency band from 10 MHz to 100 MHz and 10 nm for 1 GHz.

Characteristics and performance of offset phase locked single frequency heterodyned laser systems.

We demonstrate and characterize the performance of two heterodyned optical phase locked loop (PLL) laser systems for use in characterizing photodetector RF frequency response and nonlinearities. Descriptions of PLL circuit parameters for Nd:YAG non-planar ring oscillator lasers at 1064 nm and 1319 nm, and Er ion fiber lasers from 1530 nm to 1565 nm are presented. Both laser systems have piezoelectric transducer wavelength control over the PLL voltage controlled oscillator circuit. Offset frequency phase locking from 1.5 kHz to 51+ GHz is demonstrated. Frequency stability at 10 MHz is measured to be ±50 µHz, limited by the stability of the Rb stabilized crystal oscillator. Phase noise of the phase-locked 1319 nm laser system is discussed where we find that the phase noise is dominated by the input source noise at frequency offsets below 100 Hz and by the laser's RIN noise at frequency offsets > 100 Hz. Comparing nonlinearity data from an InGaAs p-i-n photodiode using both 1319 nm and 1550 nm PLL nonlinearity measurement systems, we find two new separate photodetector nonlinearity mechanisms. Measurements of the harmonic components of a 11 MHz sinusoidal heterodyned optical beat note signal are found to be at or below 1 nW/mW for the second harmonic (at 22 MHz) and at or below 0.25 nW/mW for the 3rd harmonic (at 33 MHz), confirming the nearly pure sinusoidal nature of the optically generated microwave beat note.

Challenges in developing new antibacterial drugs.

Regulatory guidelines for clinical development of antibacterial drugs have a major impact on decisions regarding research, influencing the degree to which novel targets are pursued, the choice of lead compounds, the spectrum of activity, as well as the dose. It is disconcerting that as pharmaceutical firms abandon antibacterial research and development, and expertise is lost from clinical, regulatory and commercial functions, biotechnology firms focus on easier, Gram-positive targets, which require limited clinical development, and expect pharmaceutical firms that have retreated from antibacterials to in-license compounds with restricted uses. Guidelines and incentives are needed to encourage development of agents targeted against the growing problem of Gram-negative bacterial resistance, as broad-spectrum drugs face even greater hurdles.

Demonstrating ecological receptor health at contaminated sites with wild rodent sperm parameters.

Consistently at Superfund and other contaminated terrestrial sites, ecological receptors have been chemically exposed for multiple decades by the time risk assessments are conducted. Given that numerous generations of the receptors have lived through the contaminated site condition by the present day, a paradigm shift from risk assessment, where the potential for health effects are forecasted, to a direct, health status assessment scheme for the site-exposed receptor, would seem to be most appropriate. We applied the only such existing direct health status assessment method, Rodent Sperm Analysis (RSA), with small rodents trapped at contaminated sites and at matched noncontaminated reference locations. Reproductive health, ecological risk assessment's endpoint of greatest concern, is targeted with RSA by comparing the sperm parameters of count, motility, and morphology, for each of which it is known how much of a change from a control condition signifies compromised reproductive capability. Given that sperm parameter thresholds were not exceeded in maximally exposed receptors, the data suggest that in the general case, contaminated terrestrial sites do not need cleanups to afford health protection to ecological species, and particularly the larger, wider-ranging, higher trophic level species. Our findings suggest that RSA has the ability to consistently discriminate between clean and contaminated sites, and that the method can allow for as definitive determinations of terrestrial ecological receptor health as are possible, thereby facilitating early site clean-up decisions.