IntroductionProphylactic replacement therapy for hemophilia A is based on intravenous infusions of purified factor VIII (FVIII) concentrates. [1][2][3][4][5][6][7][8][9][10] Since the half-life of human FVIII is about 10 to 12 hours, 11 infusions typically need to be repeated every 2 to 3 days to maintain a FVIII level above 1% in patients treated according to the pharmacokinetic (PK) dosing model. 1,[12][13][14][15] The prevention of bleeding episodes, especially in young patients, is of vital importance, as it reduces the occurrence of hemophilic arthropathy, which usually develops secondary to repeated intraarticular bleeding episodes. 3,4,6,7,[16][17][18][19][20][21] Prophylactic infusions performed in order to prevent bleeding episodes can delay the time of onset of hemophilic arthropathy and reduce the severity of pain and sequelae. Patients dosed along PK parameters usually demonstrate very few bleeding episodes and low morbidity. 22 Repeated regular intravenous infusions performed at home every 2 to 3 days over the course of decades places a great burden on patients to be compliant with their therapy. Compliance with treatment directives has been directly linked to the number of infusions given, with compliance increasing as the number of infusions decreased. 23 A FVIII molecule or product formulation that demonstrates increased time in circulation could greatly improve the efficacy and quality of life associated with prophylactic treatment for hemophilia A.The method most commonly used for prolongation of half-life of recombinant proteins, the covalent incorporation of polyethylene glycol (PEG; PEGylation), 24 is not yet available for FVIII. An alternative approach is to incorporate the FVIII protein with a carrier molecule that can be modified by PEGylation, resulting in a prolongation of the time the molecule provides hemostatic efficacy. The advantage with such an approach is that the FVIII molecule would not need to be altered and, provided that the carrier did not confer any conformational changes to the FVIII or act as an adjuvant for the immune system, the risk for FVIII inhibitor development would not be increased compared with standard treatment. Furthermore, since low levels of FVIII have been shown to confer prophylactic efficacy, the goal of maintaining FVIII levels above 1% as in the PK model may not be necessary. [25][26][27][28] Baru et al 29 reported the use of PEGylated liposomes as carriers for recombinant FVIII (Kogenate FS). Synthetic PEGylated liposomes, composed of 90% (wt/wt) palmitoyl-oleoylphosphatidylcholine (POPC) and 1,2-distearoyl-sn-glycero-3-phosphoethanol-amine-N- [poly-(ethyleneglycol) Patients, materials, and methods Study designThe study was conducted in accordance with International Conference on Harmonization Good Clinical Practice (ICH GCP) guidelines. Approval was obtained from the appropriate ethics committees as well as by the Ministry of Health. All patients gave written informed consent prior to participation. The study was designed as a controlled, patient-bl...

Optical transmission range and phase matching (PM) conditions for second harmonic generation (SHG) of Er3+:YSGG and CO2 laser in indium doped GaSe:In(0.1, 1.23, 2.32 mass%) are studied in comparison with these in pure and sulfur doped GaSe:S(0.09, 0.5, 2.2, 3 mass%) crystals. No changes in transparency curve are found in GaSe crystals up to 2.32 mass% indium content, but as small change as 0.18 degrees in PM angle for 2.79 microm Er3+:YSGG laser SHG and approximately 0.06 degrees for 9.58 microm CO2 laser emission line SHG are detected. PM properties of the crystals are evaluated as a function of temperature over the range from -165 to 230 degrees C. The value of dtheta/dT, the change in PM angle with variation of temperature, is found to be very small for GaSe:In crystals. While for SHG of Er3+:YSGG laser, dtheta/dT =22"/1 degrees C only, it is as small as -4.9"/1 degrees C for that of CO2 laser radiation. Linear variation of PM angle with temperature increasing is an indicator of absence of crystals structure transformation within temperature range from -165 to 230 degrees C. Thus, application of GaSe:In solid solutions in high average power nonlinear optical systems seems to be prospective.

In this review, we introduce the current state of the art of the growth technology of pure, lightly doped, and heavily doped (solid solution) nonlinear gallium selenide (GaSe) crystals that are able to generate broadband emission from the near infrared (IR) (0.8 mm) through the mid-and far-IR (terahertz (THz)) ranges and further into the millimeter wave (5.64 mm) range. For the first time, we show that appropriate doping is an efficient method controlling a range of the physical properties of GaSe crystals that are responsible for frequency conversion efficiency and exploitation parameters. After appropriate doping, uniform crystals grown by a modified technology with heat field rotation possess up to 3 times lower absorption coefficient in the main transparency window and THz range. Moreover, doping provides the following benefits: raises by up to 5 times the optical damage threshold; almost eliminates two-photon absorption; allows for dispersion control in the THz range independent of the mid-IR dispersion; and enables crystal processing in arbitrary directions due to the strengthened lattice. Finally, doped GaSe demonstrated better usefulness for processing compared with GaSe grown by the conventional technology and up to 15 times higher frequency conversion efficiency. INTRODUCTIONThe e-polytype of gallium selenide (hereinafter GaSe) has been known since 1934 1 and promises efficient optical frequency conversion and detection over a large range of wavelengths. The performance potential of GaSe, which belongs to the point group symmetry 6m2, can be attributed to its extreme physical properties. GaSe has a broadband transparency window over the range of 0.62-20 mm for non-polarized light continues at wavelengths o50 mm 2,3 . Other attractive physical properties of GaSe are its prodigious birefringence B 5 0.375 at l 5 10.6 mm and 0.79 at terahertz (THz) range 4 , and very high second-order nonlinear susceptibility d 22 5 54 pm V 21 at 10 mm 5 and 24.3 pm/V in the THz band 6 . Among the mid-infrared (IR) anisotropic nonlinear crystals, GaSe has the second highest optical damage threshold 7,8 and thermal conductivity in the plane of the (0001) A GaSe crystal was first used for laser frequency conversion in the mid-IR in 1972 9,10 . In subsequent years, GaSe was widely used for inlab mid-IR applications 5 . Over the past two decades, GaSe has been among the most promising nonlinear optical crystals for efficient generation of ultrabroadband radiation 0.8-5640 mm (with the

The recent focus on topological insulators is due to the scientific interest in the new state of quantum matter as well as the technology potential for a new generation of THz optoelectronics, spintronics and quantum computations. It is important to elucidate the dynamics of the Dirac fermions in the topologically protected surface state. Hence we utilized a novel ultrafast optical pump mid-infrared probe to explore the dynamics of Dirac fermions near the Dirac point. The femtosecond snapshots of the relaxation process were revealed by the ultrafast optics. Specifically, the Dirac fermion-phonon coupling strength in the Dirac cone was found to increase from 0.08 to 0.19 while Dirac fermions were away from the Dirac point into higher energy states. Further, the energy-resolved transient reflectivity spectra disclosed the energy loss rate of Dirac fermions at room temperature was about 1 meV/ps. These results are crucial to the design of Dirac fermion devices.