Visual cortex encodes timing information in humans and mice.

Despite the importance of timing in our daily lives, our understanding of how the human brain mediates second-scale time perception is limited. Here, we combined intracranial stereoelectroencephalography (SEEG) recordings in epileptic patients and circuit dissection in mice to show that visual cortex (VC) encodes timing information. We first asked human participants to perform an interval-timing task and found VC to be a key timing brain area. We then conducted optogenetic experiments in mice and showed that VC plays an important role in the interval-timing behavior. We further found that VC neurons fired in a time-keeping sequential manner and exhibited increased excitability in a timed manner. Finally, we used a computational model to illustrate a self-correcting learning process that generates interval-timed activities with scalar-timing property. Our work reveals how localized oscillations in VC occurring in the seconds to deca-seconds range relate timing information from the external world to guide behavior.

Influence of Pre-Pressing Ring on the Weld Quality of Ultrasonically Welded Short Carbon Fiber Reinforced Nylon 6 Composite.

The ultrasonic welding (UW) technique is a fast-joining process; it is very suitable for the carbon fiber reinforced thermoplastic (CFRTP) composite. For improving the consistency of the welded joint quality, a new pre-pressing ring clamp (PPRC) was designed for ultrasonic welding carbon fiber reinforced nylon composites in this paper. The effects of the PPRC on the weld quality of the ultrasonic welding welded 4.0 mm thick 30% mass short carbon fiber reinforced Nylon 6 composite was investigated and compared with that of normal clamp weld joint. The weld strength, microstructure, and temperature evolution of the joint were analyzed by tensile test, scanning electron microscope, and temperature measurement. The results showed that the PPCR UW joints had larger central weld nugget size (478 mm2 vs. 300 mm2), thicker stable fusion region thickness (1.10 mm vs. 0.96 mm), resulting in a higher joint strength (6.86 kN vs. 6.21 kN) compared with the normal clamp UW joints under the same welding parameters. The real-time monitor curve of the horn displacement and temperature at the faying interface showed that the PPRC increased the heat rating at the faying interface during instable melting stage. The PPRC could improve the contact condition between workpieces and the utilization efficiency of ultrasonic energy, which boosted the melting rate of materials at faying interface and consequently the formation of a sound joint with enough weld size (i.e., 433 mm2) in a shorter welding time (i.e., 1.3 s). Therefore, the flexibility of component assembly would be increased by the use of this sort of clamps.

Double-Pulse Ultrasonic Welding of Carbon-Fiber-Reinforced Polyamide 66 Composite.

Ultrasonic welding of thermoplastics is widely applied in automobile and aerospace industries. Increasing the weld area and avoiding thermal decomposition are contradictory factors in improving strength of ultrasonically welded polymers. In this study, relations among the loss modulus of carbon-fiber-reinforced polyamide 66 composite (CF/PA 66), time for obtaining stable weld area, and time for CF/PA 66 decomposition are investigated systematically. Then, a double-pulse ultrasonic welding process (DPUW) is proposed, and the temperature evolutions, morphologies and structures of fractured surfaces, and tensile and fatigue properties of the DPUWed joints are measured and assessed. Experimental results show the optimal welding parameters for DPUW include a weld time of 2.1 s for the first pulse, a cooling time of 12 s, and a weld time of 1.5 s for the second pulse. The DPUW process enlarged the weld area while avoided decomposition of CF/PA 66 under appropriate welding parameters. Compared to the single-pulse welded joint, the peak load, weld area, and endurance limit of the DPUWed joint increased by about 15%, 23% and 59%, respectively. DPUW also decreases the variance in strengths of the joints.

Integrated dynamic wet spinning of core-sheath hydrogel fibers for optical-to-brain/tissue communications.

Hydrogel optical light-guides have received substantial interest for applications such as deep-tissue biosensors, optogenetic stimulation and photomedicine due to their biocompatibility, (micro)structure control and tissue-like Young's modulus. However, despite recent developments, large-scale fabrication with a continuous synthetic methodology, which could produce core-sheath hydrogel fibers with the desired optical and mechanical properties suitable for deep-tissue applications, has yet to be achieved. In this study, we report a versatile concept of integrated light-triggered dynamic wet spinning capable of continuously producing core-sheath hydrogel optical fibers with tunable fiber diameters, and mechanical and optical propagation properties. Furthermore, this concept also exhibited versatility for various kinds of core-sheath functional fibers. The wet spinning synthetic procedure and fabrication process were optimized with the rational design of the core/sheath material interface compatibility [core = poly(ethylene glycol diacrylate-co-acrylamide); sheath = Ca-alginate], optical transparency, refractive index and spinning solution viscosity. The resulting hydrogel optical fibers exhibited desirable low optical attenuation (0.18 ± 0.01 dB cm-1 with 650 nm laser light), excellent biocompatibility and tissue-like Young's modulus (<2.60 MPa). The optical waveguide hydrogel fibers were successfully employed for deep-tissue cancer therapy and brain optogenetic stimulation, confirming that they could serve as an efficient versatile tool for diverse deep-tissue therapy and brain optogenetic applications.

Tracking Eye Movements During Sleep in Mice.

Eye movement is not only for adjusting the visual field and maintaining the stability of visual information on the retina, but also provides an external manifestation of the cognitive status of the brain. Recent studies showed similarity in eye movement patterns between wakefulness and rapid eye movement (REM) sleep, indicating that the brain status of REM sleep likely resembles that of awake status. REM sleep in humans could be divided into phasic REM and tonic REM sleep according to the difference in eye movement frequencies. Mice are the most commonly used animal model for studying neuronal and molecular mechanisms underlying sleep. However, there was a lack of details for eye movement patterns during REM sleep, hence it remains unknown whether REM sleep can be further divided into different stages in mice. Here we developed a device combining electroencephalogram (EEG), electromyogram (EMG) as well as eye movements recording in mice to study the eye movement patterns during sleep. We implanted a magnet beneath the conjunctiva of eye and tracked eye movements using a magnetic sensor. The magnetic signals showed strong correlation with video-oculography in head-fixed mice, indicating that the magnetic signals reflect the direction and magnitude of eye movement. We also found that the magnet implanted beneath the conjunctiva exhibited good biocompatibility. Finally, we examined eye movement in sleep-wake cycle, and discriminated tonic REM and phasic REM according to the frequency of eye movements, finding that compared to tonic REM, phasic REM exhibited higher oscillation power at 0.50 Hz, and lower oscillation power at 1.50-7.25 Hz and 9.50-12.00 Hz. Our device allowed to simultaneously record EEG, EMG, and eye movements during sleep and wakefulness, providing a convenient and high temporal-spatial resolution tool for studying eye movements in sleep and other researches in mice.

Effect of Zr content on microstructure and mechanical properties of lightweight Al2NbTi3V2Zrx high entropy alloy.

Lightweight Al2NbTi3V2Zrx (x = 1.0, 0.8, 0.6, 0.4, 0.2, 0) high entropy alloys are produced by mechanical milling and vacuum hot pressing. The microstructure, phase evolution and mechanical properties of the alloys are analyzed. The microstructure of the alloys with x = 1.0, 0.8, 0.6 consists of BCC solid solution matrix and two intermetallics (i.e., α and ß), and then ß phase disappears in Al2NbTi3V2Zr0.4 alloy. Further decreasing Zr content to below 0.2, α phase vanishes and γ and δ intermetallics emerge in Al2NbTi3V2Zr0.2 and Al2NbTi3V2 alloys. The Al2NbTi3V2Zrx alloys cannot obtain a single phase structure by decreasing Zr content with current fabrication process, which is likely because that the mixing entropy of the HEA system is not large enough to prohibit the formation of the secondary phases at hot pressing temperature of 1250 °C. All the bulks possess low density ranging from 4.93 to 5.21 g/cm3. Hardness of the Al2NbTi3V2Zrx alloys decreases from 781 HV to 697 HV and then increases to 814 HV with the decrease of Zr from x = 1 to 0. This varying tendency is closely related with the content of secondary intermetallic phases. The compressive test shows the Al2NbTi3V2Zr0.4 alloy has a yield strength of 1742 MPa, fracture strength of 2420 MPa, compressive strain of 38.2 %, which is probably related to its simplest microstructure. The comprehensive mechanical property of Al2NbTi3V2Zr0.4 alloy is superior to the majority of other HEAs and Ti64 alloy.

Effects of sitagliptin on circulating zinc-α2-glycoprotein levels in newly diagnosed type 2 diabetes patients: a randomized trial.

OBJECTIVE: Zinc-α2-glycoprotein (ZAG) has recently been characterized as a potent metabolic regulator. However, the effects of anti-diabetic agents on circulating ZAG levels in humans remain largely unknown. To explore the possible mechanisms by which the dipeptidyl peptidase-IV (DPP-IV) inhibitor improves insulin resistance, we investigated the effect of sitagliptin, a DPP-IV inhibitor, on circulating cytokine levels in newly diagnosed type 2 diabetes (nT2DM) patients. DESIGN AND METHODS: A subset of 141 subjects with nT2DM were assigned to receive placebo (n=47) or sitagliptin (n=94) for 3 months. Before and after treatment, subjects received a 75 g oral glucose tolerance test, euglycemic-hyperinsulinemic clamp (EHC), and measurement of ZAG and adiponectin (ADI) concentrations. RESULTS: Circulating ZAG levels were lower in nT2DM than in control individuals (P<0.01). After 3 months of sitagliptin treatment, HbA1c, fasting plasma glucose, postprandial glucose, 2-h insulin after glucose overload, triglycerides, and homeostasis model assessment of insulin resistance (HOMA-IR) were decreased significantly compared with pre-treatment (P<0.05 or P<0.01), whereas the glucose infusion rate during the stable period of the clamp (M values) during EHC were significantly increased (P<0.01). In addition, circulating ZAG and ADI concentrations were significantly increased along with improved glucose metabolism and insulin sensitivity compared with pre-treatment (both P<0.01) and the change of ZAG (ΔZAG) was positively associated with ΔADI, ΔHOMA-IR, ΔBMI, Δfasting insulin and negatively associated with Δ tumor necrosis factor-α (TNF-α). Furthermore, sitagliptin treatment resulted in significantly lowered plasma TNF-α level (P<0.05). CONCLUSION: A low level of circulating ZAG is associated with insulin resistance and sitagliptin treatment significantly increases circulating ZAG levels. These observations have implications in relation to the mode of action of the DPP-IV inhibitor as an insulin sensitizing agent.