THREE DIETARY PROTEIN LEVELS IN THE PRODUCTION OF SQUAB BROILERS

THREE DIETARY PROTEIN LEVELS IN THE PRODUCTION OF SQUAB BROILER

Ex-vivo HRMAS of adult brain tumours: metabolite quantification and assignment of tumour biomarkers

Background: High-resolution magic angle spinning (HRMAS) NMR spectroscopy allows detailed metabolic analysis of whole biopsy samples for investigating tumour biology and tumour classification. Accurate biochemical assignment of small molecule metabolites that are “NMR visible” will improve our interpretation of HRMAS data and the translation of NMR tumour biomarkers to in-vivo studies. Results: 1D and 2D 1H HRMAS NMR was used to determine that 29 small molecule metabolites, along with 8 macromolecule signals, account for the majority of the HRMAS spectrum of the main types of brain tumour(astrocytoma grade II, grade III gliomas, glioblastomas, metastases, meningiomas and also lymphomas). Differences in concentration of 20 of these metabolites were statistically significant between these brain tumour types. During the course of an extended 2D data acquisition the HRMAS technique itself affects sample analysis: glycine, glutathione and glycerophosphocholine all showed small concentration changes; analysis of the sample after HRMAS indicated structural damage that may affect subsequent histopathological analysis. Conclusions: A number of small molecule metabolites have been identified as potential biomarkers of tumour type that may enable development of more selective in-vivo 1H NMR acquisition methods for diagnosis and prognosis of brain tumours

Successful use of axonal transport for drug delivery by synthetic molecular vehicles

We report the use of axonal transport to achieve intraneural drug delivery. We constructed a novel tripartite complex of an axonal transport facilitator conjugated to a linker molecule bearing up to a hundred reversibly attached drug molecules. The complex efficiently enters nerve terminals after intramuscular or intradermal administration and travels within axonal processes to neuron cell bodies. The tripartite agent provided 100-fold amplification of saturable neural uptake events, delivering multiple drug molecules per complex. _In vivo_, analgesic drug delivery to systemic and to non-targeted neural tissues was greatly reduced compared to existing routes of administration, thus exemplifying the possibility of specific nerve root targeting and effectively increasing the potency of the candidate drug gabapentin 300-fold relative to oral administration

Microresonator frequency comb optical clock

Optical frequency combs serve as the clockwork of optical clocks, which are now the best time-keeping systems in existence. The use of precise optical time and frequency technology in various applications beyond the research lab remains a significant challenge, but one that integrated microresonator technology is poised to address. Here, we report a silicon-chip-based microresonator comb optical clock that converts an optical frequency reference to a microwave signal. A comb spectrum with a 25 THz span is generated with a 2 mm diameter silica disk and broadening in nonlinear fiber. This spectrum is stabilized to rubidium frequency references separated by 3.5 THz by controlling two teeth 108 modes apart. The optical clock’s output is the electronically countable 33 GHz microcomb line spacing, which features stability better than the rubidium transitions by the expected factor of 108. Our work demonstrates the comprehensive set of tools needed for interfacing microcombs to state-of-the-art optical clocks

Ultralow phase noise microwave generation with an Er:fiber-based optical frequency divider

We present an optical frequency divider based on a 200 MHz repetition rate Er:fiber mode-locked laser that, when locked to a stable optical frequency reference, generates microwave signals with absolute phase noise that is equal to or better than cryogenic microwave oscillators. At 1 Hz offset from a 10 GHz carrier, the phase noise is below -100 dBc/Hz, limited by the optical reference. For offset frequencies > 10 kHz, the phase noise is shot noise limited at -145 dBc/Hz. An analysis of the contribution of the residual noise from the Er:fiber optical frequency divider is also presented.Comment: 4 pages, 3 figure

Dual-microcavity narrow-linewidth Brillouin laser

Ultralow-noise yet tunable lasers are a revolutionary tool in precision spectroscopy, displacement measurements at the standard quantum limit, and the development of advanced optical atomic clocks. Further applications include lidar, coherent communications, frequency synthesis, and precision sensors of strain, motion, and temperature. While all applications benefit from lower frequency noise, many also require a laser that is robust and compact. Here, we introduce a dual-microcavity laser that leverages one chip-integrable silica microresonator to generate tunable 1550 nm laser light via stimulated Brillouin scattering (SBS) and a second microresonator for frequency stabilization of the SBS light. This configuration reduces the fractional frequency noise to 7.8×10^(−14)  1/√Hz at 10 Hz offset, which is a new regime of noise performance for a microresonator-based laser. Our system also features terahertz tunability and the potential for chip-level integration. We demonstrate the utility of our dual-microcavity laser by performing spectral linewidth measurements with hertz-level resolution

MCT8 expression in human fetal cerebral cortex is reduced in severe intrauterine growth restriction

The importance of the thyroid hormone (TH) transporter, monocarboxylate transporter 8 (MCT8), to human neurodevelopment is highlighted by findings of severe global neurological impairment in subjects with MCT8 (SLC16A2) mutations. Intrauterine growth restriction (IUGR), usually due to uteroplacental failure, is associated with milder neurodevelopmental deficits, which have been partly attributed to dysregulated TH action in utero secondary to reduced circulating fetal TH concentrations and decreased cerebral thyroid hormone receptor expression. We postulate that altered MCT8 expression is implicated in this pathophysiology; therefore, in this study, we sought to quantify changes in cortical MCT8 expression with IUGR. First, MCT8 immunohistochemistry was performed on occipital and parietal cerebral cortex sections obtained from appropriately grown for gestational age (AGA) human fetuses between 19 weeks of gestation and term. Secondly, MCT8 immunostaining in the occipital cortex of stillborn IUGR human fetuses at 24–28 weeks of gestation was objectively compared with that in the occipital cortex of gestationally matched AGA fetuses. Fetuses demonstrated widespread MCT8 expression in neurons within the cortical plate and subplate, in the ventricular and subventricular zones, in the epithelium of the choroid plexus and ependyma, and in microvessel wall. When complicated by IUGR, fetuses showed a significant fivefold reduction in the percentage area of cortical plate immunostained for MCT8 compared with AGA fetuses (P<0.05), but there was no significant difference in the proportion of subplate microvessels immunostained. Cortical MCT8 expression was negatively correlated with the severity of IUGR indicated by the brain:liver weight ratios (r(2)=0.28; P<0.05) at post-mortem. Our results support the hypothesis that a reduction in MCT8 expression in the IUGR fetal brain could further compromise TH-dependent brain development

Low-noise stimulated Brillouin lasing in a microrod resonator

We demonstrate a Brillouin microcavity laser based on a microrod resonator exhibiting a frequency noise of 140 HZ/√Hz at 10 Hz offset. The corresponding laser linewidth is measured to be below 400 Hz

Can Biomechanical Testing After Anterior Cruciate Ligament Reconstruction Identify Athletes at Risk for Subsequent ACL Injury to the Contralateral Uninjured Limb?

Background: Athletes are twice as likely to rupture the anterior cruciate ligament (ACL) on their healthy contralateral knee than the reconstructed graft after ACL reconstruction (ACLR). Although physical testing is commonly used after ACLR to assess injury risk to the operated knee, strength, jump, and change-of-direction performance and biomechanical measures have not been examined in those who go on to experience a contralateral ACL injury, to identify factors that may be associated with injury risk. Purpose: To prospectively examine differences in biomechanical and clinical performance measures in male athletes 9 months after ACLR between those who ruptured their previously uninjured contralateral ACL and those who did not at 2-year follow-up and to examine the ability of these differences to predict contralateral ACL injury. Study Design: Case-control study; Level of evidence, 3. Methods: A cohort of male athletes returning to level 1 sports after ACLR (N = 1045) underwent isokinetic strength testing and 3-dimensional biomechanical analysis of jump and change-of-direction tests 9 months after surgery. Participants were followed up at 2 years regarding return to play or at second ACL injury. Between-group differences were analyzed in patient-reported outcomes, performance measures, and 3-dimensional biomechanics for the contralateral limb and asymmetry. Logistic regression was applied to determine the ability of identified differences to predict contralateral ACL injury. Results: Of the cohort, 993 had follow-up at 2 years (95%), with 67 experiencing a contralateral ACL injury and 38 an ipsilateral injury. Male athletes who had a contralateral ACL injury had lower quadriceps strength and biomechanical differences on the contralateral limb during double- and single-leg drop jump tests as compared with those who did not experience an injury. Differences were related primarily to deficits in sagittal plane mechanics and plyometric ability on the contralateral side. These variables could explain group membership with fair to good ability (area under the curve, 0.74-0.80). Patient-reported outcomes, limb symmetry of clinical performance measures, and biomechanical measures in change-of-direction tasks did not differentiate those at risk for contralateral injury. Conclusion: This study highlights the importance of sagittal plane control during drop jump tasks and the limited utility of limb symmetry in performance and biomechanical measures when assessing future contralateral ACL injury risk in male athletes. Targeting the identified differences in quadriceps strength and plyometric ability during late-stage rehabilitation and testing may reduce ACL injury risk in healthy limbs in male athletes playing level 1 sports. Clinical Relevance: This study highlights the importance of assessing the contralateral limb after ACLR and identifies biomechanical differences, particularly in the sagittal plane in drop jump tasks, that may be associated with injury to this limb. These factors could be targeted during assessment and rehabilitation with additional quadriceps strengthening and plyometric exercises after ACLR to potentially reduce the high risk of injury to the previously healthy knee