Orthogonalizing the control of frequency combs for optical clockworks.

Frequency combs play a crucial supporting role for optical clocks by allowing coherent frequency division of their output signals into the electronic domain. This task requires stabilization of the comb's offset frequency and of an optical comb mode to the clock laser. However, the two actuators used to control these quantities often influence both degrees of freedom simultaneously. This non-orthogonality leads to artificial limits to the control bandwidth and unwanted noise in the comb. Here, we orthogonalize the two feedback loops with a linear combination of the measured signals in a field-programmable gate array. We demonstrate this idea using a fiber frequency comb stabilized to a clock laser at 259 THz, half the frequency of the 1S0→3P0 Yb transition. The decrease in coupling between the loops reduces the comb's optical phase noise by 20 dB. This approach could improve the performance of any comb stabilized to any optical frequency standard.

Hertz-level frequency comparisons between diverse color lasers without a frequency comb.

We present a simple yet powerful technique to measure and stabilize the relative frequency noise between two lasers emitting at vastly different wavelengths. The noise of each laser is extracted simultaneously by a frequency discriminator built around an unstabilized Mach-Zehnder fiber interferometer. Our protocol ensures that the instability of the interferometer is canceled and yields a direct measure of the relative noise between the lasers. As a demonstration, we measure the noise of a 895 nm diode laser against a reference laser located hundreds of nm away at 1561 nm. We also demonstrate the ability to stabilize the two lasers with a control bandwidth of 100 kHz using a Red Pitaya and reach a sensitivity of 1Hz2/Hz limited by detector noise. We independently verify the performance using a commercial frequency comb. This approach stands as a simple and cheap alternative to frequency combs to transport frequency stability across large spectral intervals or to characterize the noise of arbitrary color sources.

Spontaneous emulsification induced by nanoparticle surfactants.

Microemulsions, mixtures of oil, water, and surfactant, are thermodynamically stable. Unlike conventional emulsions, microemulsions form spontaneously, have a monodisperse droplet size that can be controlled by adjusting the surfactant concentration, and do not degrade with time. To make microemulsions, a judicious choice of surfactant molecules must be made, which significantly limits their potential use. Nanoparticle surfactants, on the other hand, are a promising alternative because the surface chemistry needed to make them bind to a liquid-liquid interface is both well flexible and understood. Here, we derive a thermodynamic model predicting the conditions in which nanoparticle surfactants drive spontaneous emulsification that agrees quantitatively with experiments using Noria nanoparticles. This new class of microemulsions inherits the mechanical, chemical, and optical properties of the nanoparticles used to form them, leading to novel applications.

Bidirectional microwave and optical signal dissemination.

We describe a technique to disseminate highly stable microwave and optical signals from physically separated frequency standards to multiple locations. We demonstrate our technique by transferring the frequency stability performance of a microwave frequency reference to the repetition-rate stability of an optical frequency comb in a different location. The stabilized optical frequency comb becomes available in both locations for measurements of both optical and microwave signals. We show a microwave frequency stability of 4×10(-15) in both locations for integration times beyond 100 s. The control system uses only a standard Ethernet connection.

SPTLC1 is mutated in hereditary sensory neuropathy, type 1.

Hereditary sensory neuropathy type 1 (HSN1, MIM 162400; ref. 1) genetically maps to human chromosome 9q22 (refs. 2-4). We report here that the gene encoding a subunit of serine palmitoyltransferase is located within the HSN1 locus, expressed in dorsal root ganglia (DRG) and mutated in HSN1.

Competitive reaction pathways for functionalization and volatilization in the heterogeneous oxidation of coronene thin films by hydroxyl radicals and ozone.

X-ray photoelectron spectroscopy (XPS) is used to monitor the heterogeneous reaction of hydroxyl radicals (OH) and ozone with thin films (∼5 Å) of coronene. Detailed elemental and functional group analysis of the XPS spectra reveals that there is a competition between the addition of oxygenated functional groups (functionalization) and the loss of material (volatilization) to the gas phase. Measurements of the film thickness and elemental composition indicate that carbon loss is as important as the formation of new oxygenated functional groups in controlling how the oxygen-to-carbon ratio (O/C) of the coronene film evolves during the surface reaction. When the O/C ratio of the film is small (∼0.1) the addition of functional groups dominates changes in film thickness, while for more oxygenated films (O/C > 0.3) carbon loss is an increasingly important reaction pathway. Decomposition of the film occurs via the loss of both carbon and oxygen atoms when the O/C ratio of the film exceeds 0.5. These results imply that chemically reduced hydrocarbons, such as primary organic aerosol, age in the atmosphere by forming new oxygenated functional groups, in contrast to oxygenated secondary organic aerosol, which decompose by a heterogeneous loss of carbon and/or oxygen.

Mechanistic insight into biopolymer induced iron oxide mineralization through quantification of molecular bonding.

Microbial production of iron (oxyhydr)oxides on polysaccharide rich biopolymers occurs on such a vast scale that it impacts the global iron cycle and has been responsible for major biogeochemical events. Yet the physiochemical controls these biopolymers exert on iron (oxyhydr)oxide formation are poorly understood. Here we used dynamic force spectroscopy to directly probe binding between complex, model and natural microbial polysaccharides and common iron (oxyhydr)oxides. Applying nucleation theory to our results demonstrates that if there is a strong attractive interaction between biopolymers and iron (oxyhydr)oxides, the biopolymers decrease the nucleation barriers, thus promoting mineral nucleation. These results are also supported by nucleation studies and density functional theory. Spectroscopic and thermogravimetric data provide insight into the subsequent growth dynamics and show that the degree and strength of water association with the polymers can explain the influence on iron (oxyhydr)oxide transformation rates. Combined, our results provide a mechanistic basis for understanding how polymer-mineral-water interactions alter iron (oxyhydr)oxides nucleation and growth dynamics and pave the way for an improved understanding of the consequences of polymer induced mineralization in natural systems.

Organization of cortical activities related to movement in humans.

The extent and function of synchronization of oscillatory elements in the human sensorimotor cortex during movement remains unclear. Here we determine whether synchronization is distributed in both the spatial and frequency domains and whether it changes according to task. Electrocorticographic (ECoG) signals were recorded from presumed nonpathological areas simultaneously with electromyographic (EMG) signals from upper limb muscles during isometric and phasic movement tasks in humans with subdural electrodes in situ for investigation of epilepsy. Functional mapping of the sensorimotor cortex was performed by previous electrical stimulation through the same ECoG electrodes used for recording. Significant coherence between ECoG and EMG was seen at discrete frequencies in the range of 7-100 Hz. There was no predilection for coherence within a given frequency band to be associated with cortical sites that had been functionally defined as producing contralateral arm motor responses on stimulation. However, coherence with muscle in the 7-14 and 15-30 Hz band tended to be associated with ECoG sites that lay close to or within the central sulcus as determined intraoperatively. The spatial pattern and frequency of coherence changed with different tasks, although similarities in the coherence pattern remained for tasks that shared common features. These findings provide support for the hypothesis that that synchronization at specific frequencies links cortical activities into a functional ensemble during voluntary movement.

FGF and genes encoding transcription factors in early limb specification.

SnR, twist and Fgf10 are expressed in presumptive limb territories of early chick embryos. When FGF-2/FGF-8 beads are implanted in chick flank, an ectopic limb develops and SnR is irreversibly activated as early as 1 h. Ectopic Fgf10 and twist expression are activated much later at 17 and 20 h, respectively. FGF-10 can also induce SnR, but much later, and in this case activation occurs simultaneously with that of twist and Fgf10 via the Fgf8- expressing ridge. Tbx-4 and Tbx-5 are expressed in leg and wing forming regions, respectively, in a similar pattern to SnR and twist. FGF-2 leads to ectopic expression of Tbx-4 and Tbx-5 as rapidly as ectopic expression of SnR, but the patterns of ectopic transcripts suggest that induction of SnR and Tbx gene expression occur via different pathways.

Disulfiram neuropathy.

A 35-year-old man developed a distal sensorimotor polyneuropathy after taking disulfiram, 500 mg daily for five months. His symptoms improved after the drug therapy was discontinued. Clinical, electrophysiological, and pathological observations during the acute stage and during recovery suggest that disulfiram produces a distal axonopathy.

Inhibition in the human motor cortex is reduced just before a voluntary contraction.

OBJECTIVE: To examine inhibition in the human motor cortex before and during voluntary movements. METHODS: The balance between the excitation and inhibition of corticospinal neurons in the human motor cortex was tested by conditioning the motor evoked potentials (MEP) evoked in forearm muscles by transcranial magnetic stimulation with a preceding subthreshold stimulus delivered through the same coil. RESULTS: When normal individuals (n = 9) made a tonic wrist extension, inhibition of the forearm extensor MEP decreased, whereas that of the forearm flexors was unchanged. When these individuals made a tonic wrist flexion, inhibition of the forearm flexor MEP diminished, whereas that of the forearm extensors was unchanged. When normal individuals (n = 10) made a phasic wrist extension in response to an auditory signal, inhibition of the extensor MEP began to decline about 95 msec before the onset of the agonist EMG activity. CONCLUSIONS: The changes in balance of excitation and inhibition of corticospinal neurons associated with a voluntary movement precede the movement and are directed at the corticospinal neurons projecting to the agonists. These changes may help to select the population of cortical neurons responsible for the movement.

Reciprocal inhibition in cerebral palsy.

We studied reciprocal inhibition by recording the changes in firing probability of single motor units of the tibialis anterior muscle following stimulation of low-threshold afferents in the posterior tibial nerve. In 15 patients with cerebral palsy, the inhibition was as great or greater than normal. We found no evidence that group I afferents produce "reciprocal facilitation" in cerebral palsy.

Neurophysiologic changes in hemiplegia. Possible explanation for the initial disparity between muscle tone and tendon reflexes.

In an attempt to clarify the neurophysiologic changes that may follow a cerebral lesion in man, we have studied patients with recent and with long-standing hemiplegia from cerebral infarction. In patients with recent cerebral lesions, inhibition of the monosynaptic reflex by vibration is enhanced. In patients with long-standing cerebral lesions, this inhibitory mechanism is less effective and a comparison of the electrically and mechanically induced monosynaptic reflexes suggests that fusimotor drive may be increased. Related clinical findings are reduced muscle "tone" immediately after the lesion and increased muscle "tone" and exaggerated tendon jerks in patients with long-standing hemiplegia.

Neurophysiologic aspects of deep brain stimulation.

Implanting electrodes for deep brain stimulation (DBS) allows performance of a number of different neurophysiologic studies. Before definitive internalization of the device, recording and stimulation through the electrodes is possible. Stimulation of the globus pallidum produced a mixture of excitation and inhibition of ongoing muscle activity. The excitatory response is probably produced by activation of the large-diameter fibers of the corticospinal tract. Stimulation of the thalamus is mainly associated with EMG inhibition. These findings indicate that the effect of stimulation may vary in different targets and that the mechanism of action of DBS is heterogeneous. A different type of study concerns those undertaken after chronic DBS of the subthalamic nucleus (STN) and globus pallidum internum (GPi) in parkinsonian patients. Cortical mechanisms subserving movement preparation and execution have been assessed. The main findings were that stimulation had a more prominent effect on execution than on preparation and that this was greater in patients treated with STN DBS than GPi DBS.

Reflex effects from Golgi tendon organ (Ib) afferents are unchanged after spinal cord lesions in humans.

The reflex actions of medial gastrocnemius (MG) group I afferents on soleus motoneurons were examined in 20 normal subjects and 13 patients with well-defined chronic spinal cord lesions. In normal subjects, stimulation of the MG nerve with near-nerve electrodes at or below the threshold of the alpha motoneuron axons resulted in inhibition of the soleus H reflex at a condition-test interval of 6 msec. The central delay was estimated to be 2.5 msec. This inhibition was attributed to Ib afferents. We found that this inhibition was present in patients with spinal cord lesions. This contrasts with previous reports that stimulation of MG afferents facilitates the soleus H reflex in hemiplegic limbs, and it may represent a physiologic difference between cerebral and spinal spasticity.

Associated postural adjustments are impaired by a lesion of the cortex.

A ballistic movement of one arm may be accompanied by contractions of contralateral postural muscles known as "associated postural adjustments." Ballistic movements are considered to involve the motor cortex, but it is not known where associated postural adjustments are generated. We recorded the EMG activity in the deltoid and latissimus dorsi muscles during ballistic abduction of the arm in 10 normal subjects and five subjects with lesions of the motor cortex. When subjects with cortical lesions abducted the unaffected arm, the associated postural adjustment in the contralateral latissimus dorsi was significantly smaller than normal. We argue that postural adjustments, like ballistic movements, require the participation of the motor cortex.

On the cause of hyporeflexia in the Holmes-Adie syndrome.

Electrophysiologic studies were carried out on 11 patients with Holmes-Adie syndrome, 8 of whom had reduced or absent ankle jerks. Conduction velocities and evoked nerve and muscle compound action potentials in the peroneal, posterior tibial, and sural nerves were normal. The H reflex was absent (or virtually absent) in the patients with depressed reflexes. The amplitude of the composite Ia EPSP in single soleus motoneurons was estimated from changes in firing probability of voluntarily activated soleus motor units in response to stimulation of low threshold afferents in the tibial nerve. These amplitudes were used to test the afferent side of the reflex pathway. Composite group Ia EPSPs in Holmes-Aide patients with hyporeflexia were smaller than normal or absent, indicating that the areflexia in the Holmes-Aide syndrome is due to loss of large spindle afferents or reduced effectiveness of their monosynaptic connections to motoneurons.

Cortical-basal ganglionic degeneration.

We report our experience with 15 patients believed to have cortical-basal ganglionic degeneration. The clinical picture is distinctive, comprising features referable to both cortical and basal ganglionic dysfunction. Characteristic manifestations include cortical sensory loss, focal reflex myoclonus, "alien limb" phenomena, apraxia, rigidity and akinesia, a postural-action tremor, limb dystonia, hyperreflexia, and postural instability. The asymmetry of symptoms and signs is often striking. Brain imaging may demonstrate greater abnormalities contralateral to the more affected side. Postmortem studies in 2 patients revealed the characteristic pathologic features of swollen, poorly staining (achromatic) neurons and degeneration of cerebral cortex and substantia nigra. Biochemical analysis of 1 brain showed a severe, diffuse loss of dopamine in the striatum. This condition is more frequent than previously believed, and the diagnosis can be predicted during life on the basis of clinical findings. However, as with other "degenerative" diseases of the nervous system, a definitive diagnosis of cortical-basal ganglionic degeneration requires confirmation by autopsy.

Effect of intravenous sodium amytal on cutaneous limb temperatures and sympathetic skin responses in normal subjects and pain patients with and without Complex Regional Pain Syndromes (type I and II). I.

This study examined the effects of intravenous administration of sodium amytal (SA), a medium action barbiturate, on cutaneous limb temperatures and sympathetic skin responses (SSR) to electrical stimulation. Eight normal volunteers and 13 patients with musculoskeletal pain, somatoform pain disorders or nerve/root injury (with findings strictly limited to the distribution of the distribution of the involved nerve) were compared to 15 patients with Complex Regional Pain syndromes (one of whom had documented nerve injury). The Complex Regional Pain Syndromes (CRPS) patients were characterized by the presence of severe diffuse limb pain and extraterritorial sensory, sudomotor and vasomotor abnormalities (i.e., not confined to the site of injury or the distribution of the injured nerve). The CRPS patients were different from the normal controls and the non-CRPS patients in their tendency to warm significantly many of their limbs (not just the symptomatic ones). SSR were reduced or lost in a few limbs only in all three groups, irrespective of the increase or decrease of limb temperature and the side of symptoms. We argue that the enhanced thermogenic effect of SA in CRPS patients is due to generalized central changes of thermoregulatory control specifically in this group.

How synaptic noise may affect cross-correlations.

The relationship between a postsynaptic potential (the 'test PSP') and the profile of the cross-correlation that it produces in a repetitively discharging mammalian motoneuron, with and without synaptic noise, has been explored by computer stimulation. In a noiseless motoneuron the cross-correlation profile represents the first derivative of PSP shape except where 'shadowing' occurs (Eqn. 1a-c). When synaptic noise is present the relationship changes. When the amplitude of spike-like 'noise PSPs' occurring at regular intervals reaches a critical value (Eqn. 2), all threshold crossings involve noise PSPs. Under these circumstances termed 'just maximally effective synaptic noise', the cross-correlation represents test PSP directly (Eqn. 3a). When the interval between noise PSPs is shortened the relationship reverts to the first differential (Eqn. 4a-c). If the amplitude of the noise PSPs is less than the critical value (Eqn. 5) the cross-correlation profile is represented in a complex way by a combination of the first derivative of the upper part and the direct representation of the lower part of the test PSP. The area of the cross-correlation peak above baseline provides the most reliable estimate of EPSP amplitude in a noiseless motoneuron (Eqn. 6a). This area may fall to half for the same triangular test EPSP in the presence of just maximally effective synaptic noise (Eqn. 7a). In general, the presence of synaptic noise leads to underestimation of EPSP amplitude. These general principles remain valid for physiological noise consisting of randomly occurring EPSPs and allow certain experimental findings in cat motoneurons to be understood.