Abstract:
An apparatus can be provided which can include a laser arrangement which can be configured to provide a laser radiation, and can include an optical cavity. The optical cavity can include a dispersive optical first arrangement which can be configured to receive and disperse at least one first electro-magnetic radiation so as to provide at least one second electro-magnetic radiation. Such cavity can also include an active optical modulator second arrangement which can be configured to receive and modulate the at least one second radiation so as to provide at least one third electro-magnetic radiation. The optical cavity can further include a dispersive optical third arrangement which can be configured to receive and disperse at least one third electro-magnetic radiation so as to provide at least one fourth electro-magnetic radiation. For example, actions by the first, second and third arrangements can cause a spectral filtering of the fourth electro-magnetic radiation(s) relative to the first electro-magnetic radiation(s). The laser radiation can be associated with the fourth radiation(s), and a wavelength of the laser radiation can be controlled by the spectral filtering caused by the actions by the first, second and third arrangements.

Description:
CROSS-REFERENCE TO RELATED APPLICATION(S) 
     The present application relates to and claims the benefit and priority from International Patent Application No. PCT/US2014/048256 filed on Jul. 25, 2014, which claims the benefit and priority from U.S. Provisional Patent Application Ser. No. 61/858,808, filed Jul. 26, 2013, the entire disclosures of which are incorporated herein by reference. 
    
    
     STATEMENT OF FEDERAL SUPPORT 
     The present disclosure was made with U.S. Government support under grant number FA9550-11-1-0331 from the Department of Defense, United States Air Force, Office Of Scientific Research. Thus, the Government has certain rights to the disclosure described and claimed herein. 
    
    
     FIELD OF THE DISCLOSURE 
     The present disclosure relates to optical imaging systems, and more particularly to methods, systems and apparatus which can provide and/or utilize optical sources that have varying wavelengths for use in, e.g., Fourier-domain optical coherence tomography. 
     BACKGROUND INFORMATION 
     The potential of optical coherence tomography (OCT) configuration which can be used with a diagnostic tool/method/apparatus is capable of providing high-resolution cross-sectional images of tissue microstructure to depths of 2 mm has been well appreciated for over a decade. Many exemplary OCT systems and methods utilize a laser source with a wavelength output that changes over time. Various technologies have been described to provide such wavelength-tunable laser source. Such lasers generally include an element that selects for a specific wavelength. For example, in some optical source designs a spectral filter is incorporated into a laser cavity, and this spectral filter is configured to vary its spectral filtering properties over time [REFS]. In other designs, the laser cavity length can be modulated to affect its output wavelength [REFS]. In such designs, the rate at which the laser can change its output wavelength is a function of the rate at which the spectral filter or cavity length can be changed. In various configurations, the spectral filter or cavity length is changed through mechanical actuation, and is therefore likely limited in its rate of change by mechanical forces such as inertia. 
     Accordingly, there may be a need to address at least some of the above-described deficiencies. 
     SUMMARY OF EXEMPLARY EMBODIMENTS 
     Thus, to address at least such issues and/or deficiencies, exemplary embodiments of methods, systems and apparatus which can provide and/or utilize optical sources that have varying wavelengths for use in, e.g., Fourier-domain optical coherence tomography can be provided. 
     According to one exemplary embodiment, methods, systems and apparatus which can provide and/or utilize optical sources optical sources that can utilize, e.g., chromatically dispersive elements and/or arrangement to enable wavelength-varying optical sources. A chromatically dispersive element and/or arrangement can be configured to have differing propagation times for different wavelengths. Because the dispersive element and/or arrangement do not require a mechanical actuation, it can be used to create, facilitate and/or provide sources whose wavelength changes rapidly. 
     Accordingly, an exemplary apparatus can be provided which can include a laser arrangement which can be configured to provide a laser radiation, and can include an optical cavity. The optical cavity can include a dispersive optical first arrangement which can be configured to receive and disperse at least one first electro-magnetic radiation so as to provide at least one second electro-magnetic radiation. Such cavity can also include an active optical modulator second arrangement which can be configured to receive and modulate the at least one second radiation so as to provide at least one third electro-magnetic radiation. The optical cavity can further include a dispersive optical third arrangement which can be configured to receive and disperse at least one third electro-magnetic radiation so as to provide at least one fourth electro-magnetic radiation. For example, actions by the first, second and third arrangements can cause a spectral filtering of the fourth electro-magnetic radiation(s) relative to the first electro-magnetic radiation(s). The laser radiation can be associated with the fourth radiation(s), and a wavelength of the laser radiation can be controlled by the spectral filtering caused by the actions by the first, second and third arrangements. 
     In one exemplary embodiment of the present disclosure, the second arrangement can be and/or include an amplitude modulator, a phase modulator and/or a polarization modulator. An induced dispersion caused by the third arrangement can be approximately equal in magnitude and opposite in sign to an induced dispersion caused the first arrangement over an operating optical bandwidth of the laser arrangement. In addition, the optical cavity can include a fixed periodic spectral filter arrangement. The fixed periodic spectral filter arrangement can be or include a Fabry-Perot etalon filter. 
     According to another exemplary embodiment of the present disclosure, the laser radiation can have a wavelength that changes over time. For example, the actions by the first, second and third arrangements can cause the wavelength to change at a rate that is faster than 80 nm/microsec. Further or alternatively, the actions by the first, second and third arrangements can cause the wavelength to change in discrete steps. The discrete steps can be shorter than 100 nsec. 
     In yet another exemplary embodiment of the present disclosure, a generator can be provided which can be configured to control and/or drive the second arrangement. The generator can include and/or be a pulse generator, a pattern generator and/or a waveform generator. The first arrangement and/or a third arrangement includes a further active optical modulator arrangement that can be different from the second arrangement. At least one optical amplifier arrangement can also be provided, which can be configured to amplify the first radiation, the second radiation, the third radiation and/or the laser radiation. The optical amplifier arrangement can include or be a semiconductor amplifier, a Raman amplifier, a parametric optical amplifier and/or a fiber amplifier. 
     These and other objects, features and advantages of the present disclosure will become apparent upon reading the following detailed description of exemplary embodiments of the present disclosure, when taken in conjunction with the appended drawings and claims. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
       Further objects, features and advantages of the invention will become apparent from the following detailed description taken in conjunction with the accompanying figures showing illustrative embodiments of the present disclosure, in which: 
         FIG. 1  is a block diagram a system which includes an optical source whose wavelength varies with time, according to an exemplary embodiment of the present disclosure; 
         FIG. 2A  is a block diagram of a pulsed wavelength source arrangement associated with or provided in the system of  FIG. 1 , according to an exemplary embodiment of the present disclosure; 
         FIG. 2B  is a graph of an exemplary optical comb spectrum generated by the exemplary arrangement of  FIG. 2A ; 
         FIG. 3A  is a block diagram of another system according to a further exemplary embodiment of the present disclosure in which positive and negative chromatically dispersive elements can be provided in a laser cavity to generate a wavelength varying laser output; 
         FIG. 3B  is a plot of a resulting laser output power generated by the system of  FIG. 3A  versus time; 
         FIG. 4A  is a diagram of an subband delay equalizer of the system shown in  FIG. 3A , in according to yet another exemplary embodiment of the present disclosure; 
         FIG. 4B  is a diagram of the subband delay equalizer of the system shown in  FIG. 3A , in according to a further exemplary embodiment of the present disclosure; 
         FIG. 5  is a block diagram of a source arrangement associated with or provided in the system of  FIG. 1 , according to still another exemplary embodiment of the present disclosure; 
         FIG. 6  is a block diagram illustrating a wavelength-stepped laser system according to another exemplary embodiment of the present disclosure; and 
         FIG. 7  is a block diagram illustrating the wavelength-swept laser system according to still another exemplary embodiment of the present disclosure; and 
         FIGS. 8A and 8B  are graphs illustrating measured laser outputs of the exemplary wavelength-stepped laser in the spectrum domain and the time domain, respectively, at different mirror distance in air; and 
         FIGS. 9A and 9B  are graphs illustrating representative laser outputs of the exemplary wavelength-swept laser in the spectrum domain and the time domain, respectively at different mirror distance in air. 
     
    
    
     Throughout the drawings, the same reference numerals and characters, if any and unless otherwise stated, are used to denote like features, elements, components, or portions of the illustrated embodiments. Moreover, while the subject disclosure will now be described in detail with reference to the drawings, it is done so in connection with the illustrative embodiments. It is intended that changes and modifications can be made to the described exemplary embodiments without departing from the true scope and spirit of the subject disclosure and appended claims. 
     DETAILED DESCRIPTION OF EXEMPLARY EMBODIMENTS 
       FIG. 1  shows an illustration of an optical source whose wavelength varies with time, according to an exemplary embodiment of the present disclosure. The exemplary source includes a pulsed multi-wavelength source  100  followed by a chromatically dispersive element  110 . The optical pulse  120  output from the pulsed source  100  can include multiple wavelengths and can either contain a continuous spectrum of light, for example, from an amplified spontaneous light source, or can contain discrete wavelengths for example from an optical comb source. This optical pulse travels through the dispersive element  110 . An output pulse  130  can be created and/or generated which can be spread in time, and each time within the pulse can include a subset of the wavelengths contained within the original pulse  120 . Thus, by measuring the leading edge of the pulse, the wavelengths that have propagated faster through the system can be measured. The exemplary output pulse  130  can be used as a wavelength swept or wavelength stepped optical source pulse in the Fourier-domain OCT. The dispersive element  110  in this exemplary system can be any or a combination of, e.g., an optical fiber, a dispersion-compensating optical fiber, a photonic crystal fiber, a chirped fiber Bragg grating (FBG), a grating-based dispersive path, etc. 
     According to an exemplary embodiment of the present disclosure, the pulsed wavelength source  100  can comprise and/or be a continuous wave broadband light source that can be spectrally filtered (e.g., optionally amplified), and then directed to an intensity modulator to create and/or generate the pulse. Alternatively or in addition, the spectral filter can be removed if a continuous spectral source is utilized. 
     An exemplary embodiment of the pulsed wavelength source according to the present disclosure is illustrated in  FIG. 2A . As shown in  FIG. 2A , an Amplified Spontaneous Emission (ASE) light source  150  can be used to generate the broadband continuous wave light. Such light can be collimated using two or more collimators  151 ,  152 , and configured to be transmitted through a Fabry-Perot (FP) etalon  160  to achieve spectral filtering. This can, for example, create and/or generate an optical comb spectrum  177  which can be defined by a periodic optical power  175  versus wavenumber  176 , as shown in the graph of  FIG. 2B . Turning to  FIG. 2A , this light can be amplified by an amplifier  165  which can be or include, e.g., a semiconductor optical amplifier, a doped-fiber amplifier, a Raman amplifier, or other optical amplifiers. Further, the light output from the amplifier  165  can be directed to an intensity modulator  166  which can be of include, for example, a Lithium Niobate modulator, among others. The resulting pulse  170  can be used as the multi-wavelength pulsed source arrangement  120  shown in  FIG. 1 . 
     In another exemplary embodiment of the present disclosure, positive and negative chromatically dispersive elements can be provided in a laser cavity to generate a wavelength varying laser output. For example, as shown in  FIG. 3A , a laser cavity can be configured and/or structured to contain or include an intensity modulator  510 , a positive dispersive element/arrangement  515 , an optional subband delay equalizer  516 , an amplifier  520 , a coupler  525 , and a negative dispersive element/arrangement  530 . The intensity modulator  510  can be driven to be optically transmissive for a short duration, tau, and this transmission can be repeated periodically. A generated optical pulse  550   a  can include multiple wavelengths, and directed to the positive dispersive element  515 , where the wavelengths can, in part, be separated in time through pulse spreading effects. 
     If a subband delay equalizer  516  is not included in the exemplary configuration, a pulse  550   b  can be directed to the optical amplifier  520 , where each wavelength can be amplified. This amplifier  520  could be or include, e.g., a semiconductor optical amplifier, a doped fiber amplifier, or a Raman amplifier, among others. Further, if Raman amplification is used, the amplification can be performed, in part, within a dispersive fiber that can be part of the dispersive elements/arrangements  515  or  530 . The amplified light or radiation  550   c  can then be directed to the coupler  525 , which can direct a portion to the laser output  535  and a portion to the negative dispersive element/arrangement  530 . The negative dispersive element/arrangement  530  can be configured to compress such dispersed pulse to approximately its shape before it enters the positive dispersive element/arrangement  515 . A compressed pulse  550   d  can be directed to the intensity modulator  510 , and the intensity modulator  510  can be driven such that this pulse is substantially transmitted. In such exemplary configuration, the order of elements can be changed, and  FIG. 2A  illustrates only one exemplary ordering of various possible elements and connections. A plot  562  of a resulting laser output power  561  provided by the exemplary system of  FIG. 3A  versus time  560 , as shown in  FIG. 3B , indicates a wavelength varying nature thereof. 
     According to yet another exemplary embodiment of the present disclosure, the positive dispersive element/arrangement and negative dispersive elements/arrangements can be or include optical fibers which can be configured to have approximately equal and opposite chromatic dispersions across a wavelength range. In a further exemplary embodiment of the present disclosure, the subband delay equalizer  516  can be included to correct for variations in total optical propagation time through the positive dispersive element/arrangement  515  and the negative dispersive element/arrangement  530  with a wavelength. 
     In still another exemplary embodiment of the present disclosure, as shown in  FIG. 4A , the subband delay equalizer  516  can constructed from a set of distinct reflective paths  600 . For example, as shown in  FIG. 4A , the light or other radiation can enter the subband delay equalizer at path  601 , and can be directed to an optical circulator  603 , where such light/radiation can be directed to a coupling arrangement  605  that can generate multiple outputs  606   a ,  606   b ,  606   c ,  606   d . The coupling arrangement  605  can be configured to divide the input light/radiation into distinct paths according to, e.g., one or more wavelengths using, for example, wavelength-division multiplexing. Each optical path can be terminated by a reflective element/arrangement  610   a ,  610   b ,  610   c ,  610   d  (e.g., a mirror), and the optical path length between these elements/arrangements  610   a ,  610   b ,  610   c ,  610   d  and the coupling arrangement  605  can be configured to induce distinct optical propagations delays on each path. These exemplary delays can be used to adjust the overall optical propagation delay through the laser cavity for each wavelength band. Returned light/radiation can be transmitted by the optical circulator  603  to the output  602  of the subband delay equalizer  516 . 
     In a still further exemplary embodiment of the present disclosure, as shown in  FIG. 4B , the subband delay equalizer  516  (which can be constructed from a set of further reflective paths  650 ) can comprise an input  651  that can direct the light/radiation to an optical circulator  653  which directs light to a collimator  655 . The collimated beam is made to interact with a set of low-pass optical reflector arrangements  660   a ,  660   b ,  660   c ,  660   d  (e.g., mirrors) located along the beam path, facilitating wavelength bands to return to the circulator  653  with, e.g., differing optical transit times depending on which reflecting arrangement that wavelength reflected from, and where such respective reflecting arrangement is located relative to the collimator  655 . The reflected light/radiation can then be directed by the optical circulator  653  to an output  652  such that the optical delay through the subband delay equalizer  650  is wavelength dependent and configurable. The reflecting arrangements  660   a ,  660   b ,  660   c ,  660   d  can provide low-pass, band-pass or high-pass functionality, and can be or include, for example, dichroic mirrors and/or fiber Bragg gratings. 
     In another exemplary embodiment of the present disclosure, the exemplary source arrangement of  FIG. 2A  can include a spectral filter to generate a set of discrete wavelengths, rather than a continuously varying wavelength response. This spectral filter can be or include, for example, a Fabry-Perot etalon, and can be provided or positioned at any location within the laser cavity. For an exemplary operation of the exemplary source arrangement of  FIG. 2A , the pulse width can be in the range of about 0.1 ns to 1 ns, and the magnitude of the dispersion induced by the positive and negative dispersive elements/arrangements can be from about 200 ps/nm to 2000 ps/nm. 
     According to a further exemplary embodiment of the present disclosure, another exemplary source arrangement (e.g., a laser arrangement) can be provided, as illustrated in  FIG. 5 . The exemplary source arrangement of  FIG. 5  can comprise a first optical phase modulator  710  and a second optical phase modulator  720 . These exemplary phase modulators  710 ,  720  can be or include, for example, Lithium Niobate phase modulators. The exemplary source arrangement can also include a dispersive element/arrangement  715 , an output coupler  722 , a Fabry Perot etalon  725 , and a compensating dispersive element/arrangement  730  with a dispersion that can be substantially equal and opposite to that provided by the dispersive element/arrangement  715 . 
     In exemplary operation, the first phase modulator  710  can be driven by a first electrical signal  761 , and the second phase modulator  720  can be driven by a second signal  762 . The first light/radiation transmitted through the Fabry Perot etalon  725  can be arranged in spectral lines with a narrow instantaneous linewidth in each line. The first phase modulator  710  can induce a modulation on each line that spectrally broadens each such line. Each pulse can then travel through the dispersive element  715  to the second phase modulator  720 . Because of its chromatic dispersion, each signal can reach the second phase modulator  720  at a time that is dependent on its wavelength. If the second signal  762  is opposite to the first signal  761  for a given delay, then the wavelength that has a travel-time between the first phase modulator  710  and the second phase modulator  720  can have its broadening undone, while the others will experience a further broadening by the second phase modulator  720 . Thus, e.g., only the wavelength that has been re-narrowed can transmit through the Fabry Perot  725  with a high efficiency, and this wavelength would likely be that of the laser. Thus, by adjusting the first and second signals  761 ,  762 , the lasing wavelength can be selected. If these signals are rapidly modulated, the source arrangement can be made to rapidly switch wavelengths among the transmissions modes of the Fabry Perot etalon  725 , thereby achieving a wavelength-varying output at an output  750 . 
       FIG. 6  shows a block diagram of a wavelength-stepped laser source system, according to an exemplary embodiment of the present disclosure, that provides time-varying output wavelengths, e.g., substantially equally spaced in wavenumber. The exemplary source system can include a Fabry-Perot (FP)  1020  etalon with free spectral range of, e.g., about 200 GHz and finesse of about 100, approximately 39.394 km chromatic dispersive fiber (smf28e)  1030  providing approximately 680 ps/nm dispersion, a dispersion compensating fiber  1070  providing nominally approximately −680 ps/nm dispersion and designed/configured to be a dispersion slope match to the dispersive fiber  1030 , approximately &gt;30 dB extinction lithium niobate intensity modulator  1040 , and two or more semiconductor optical amplifiers  1080   a ,  1080   b . A further semiconductor optical amplifier  1080   c  outside the laser cavity can also be included and used to increase power and reduce intensity noise. A polarization state of the transmitted light (or other electro-magnetic radiation) provided via, e.g., a single mode fiber, can be altered by polarization controllers  1010   a ,  1010   b ,  1010   c ,  1010   d , and  1010   e  for maximum transmission and/or gain. For example, a 10% tap output couple  1090  can be included that can provide the laser output (or an output of another electro-magnetic radiation). An analog pulse generator  1050  can also be provided that can be configured to generate approximately 0.50 ns full-width at half-maximum pulses. The exemplary wavelength-stepped laser source system can also include digital delay generator  1060  which can be configured to externally trigger the pulse generator  1050 . Two or more collimators  1095   a ,  1095   b  can be used to generate collimated light transmitted through a Fabry-Perot (FP)  1020  etalon to achieve, e.g., a spectral spacing of about 200 GHz (1.6 nm). The wavelength-stepped source system can also include a Fabry-Perot etalon with smaller free spectral range that can be in the range of about 0.1 GHz to 10,000 GHz. Additional dispersive elements can be included in the cavity, e.g., to improve the matching between the positive and negative dispersive arrangements. Additionally, other dispersive elements, such as, e.g., chirped fiber Bragg gratings, can be used to provide positive or negative dispersion. 
     According to yet another embodiment of the present disclosure, it is also possible to provide a rapid wavelength-swept source system for effectuating a Fourier-domain Optical Coherence Tomography. For example, a removal of the intracavity Fabry-Perot etalon can facilitate a continuous spectral operation.  FIG. 7  shows a block diagram of the wavelength-swept laser source system that provides time-varying output wavelengths continuously in wavenumber according to a further exemplary embodiment of the present disclosure. The exemplary source system illustrated in  FIG. 7  can include a 39.394 km chromatic dispersive fiber (smf28e)  2015 , a dispersion compensating fiber  2055  designed and/or configured to be dispersion slope match to a chromatic dispersive fiber  2015 , a &gt;30 dB extinction lithium niobate intensity modulator  2025 , and two semiconductor optical amplifiers  2065   a ,  2065   b . For example, approximately 10% tap output couple  2075  can provide the laser output (or output of another electro-magnetic radiation). Another semiconductor optical amplifier  2065   c  outside the laser cavity can be provided and utilized to increase power and reduce intensity noise. A polarization state of the transmitted light (or other electro-magnetic radiation) through, e.g., a single mode fiber can be altered by polarization controllers  2005   a ,  2005   b ,  2005   c ,  2005   d , and  2005   e  for maximum transmission and gain. An analog pulse generator  2035  can be used to generate approximately 0.50 ns full-width at half-maximum pulses. A digital delay generator  2045  can be used to externally trigger the pulse generator  2035 . 
     The output spectrum of the wavelength-stepped laser system indicates a spectral comb structure forced by the 200 GHz (1.6 nm) free spectral range Fabry-Perot etalon, as shown in  FIG. 8A  in an exemplary graph  5000   a . For example, the lasing bandwidth can be measured to be about 94 nm. The laser output (or other electro-magnetic radiation) in the time domain at a repetition rate of over 9 MHz is shown in  FIG. 8B  as a graph  5000   b . Such exemplary rate can be increased up to 100 MHz with suitable electronic drive signals. The exemplary generation of temporally separated optical pulses for each wavelength is also shown in  FIGS. 8A and 8B  with, e.g., approximately 2 GHz receiver bandwidth limitations. The exemplary source system can be operated at, e.g., about 54% duty cycle. The exemplary duty cycle can be increased/decreased by changing the pulse generation rate with components of the digital delay generator  1060  and/or the pulse generator  1050  of  FIG. 6 . The illustrated source system can be run at, e.g., approximately 20 MHz repetition rates with a duty cycle near 100%. The exemplary operation can also be run at other repetition rates, as should be understood by those having ordinary skill in the art. 
       FIGS. 9A and 9B  illustrate exemplary graphs providing exemplary results that characterize the exemplary wavelength-swept laser source system of  FIG. 7 . For example,  FIG. 9A  shows an exemplary optical spectrum-tracing graph  6000   a  illustrating an optical bandwidth of, e.g., about 87 nm. This exemplary spectral bandwidth can be increased and/or decreased by, e.g., adjusting the gain medium, duty cycle of the intensity modulator, and/or the matching of the dispersion fibers  2015  and  2055  shown in  FIG. 7 .  FIG. 9  shows an exemplary graph  6000   b  of an expected continuous shape of the exemplary output of the exemplary laser system, e.g., with about 9 MHz repetition rate. 
     The foregoing merely illustrates the principles of the disclosure. Various modifications and alterations to the described embodiments will be apparent to those skilled in the art in view of the teachings herein. Indeed, the arrangements, systems and methods according to the exemplary embodiments of the present disclosure can be used with and/or implement any OCT system, OFDI system, SD-OCT system or other imaging systems, and for example with those described in International Patent Application PCT/US2004/029148, filed Sep. 8, 2004 which published as International Patent Publication No. WO 2005/047813 on May 26, 2005, U.S. patent application Ser. No. 11/266,779, filed Nov. 2, 2005 which published as U.S. Patent Publication No. 2006/0093276 on May 4, 2006, and U.S. patent application Ser. No. 10/501,276, filed Jul. 9, 2004 which published as U.S. Patent Publication No. 2005/0018201 on Jan. 27, 2005, and U.S. Patent Publication No. 2002/0122246, published on May 9, 2002, the disclosures of which are incorporated by reference herein in their entireties. It will thus be appreciated that those skilled in the art will be able to devise numerous systems, arrangements and methods which, although not explicitly shown or described herein, embody the principles of the disclosure and are thus within the spirit and scope of the present disclosure. It should be understood that the exemplary procedures described herein can be stored on any computer accessible medium, including a hard drive, RAM, ROM, removable disks, CD-ROM, memory sticks, etc., and executed by a processing arrangement and/or computing arrangement which can be and/or include a hardware processors, microprocessor, mini, macro, mainframe, etc., including a plurality and/or combination thereof. In addition, certain terms used in the present disclosure, including the specification, drawings and claims thereof, can be used synonymously in certain instances, including, but not limited to, e.g., data and information. It should be understood that, while these words, and/or other words that can be synonymous to one another, can be used synonymously herein, that there can be instances when such words can be intended to not be used synonymously. Further, to the extent that the prior art knowledge has not been explicitly incorporated by reference herein above, it can be explicitly incorporated herein in its entirety. All publications referenced herein can be incorporated herein by reference in their entireties.