The endogenous enhancement of antioxidants in a human being has the ability to reduce free radicals. Free radicals are linked to cell damage associated with aging and a wide variety of diseases. Exogenous administration of antioxidants has safety risks given that appropriate dosage levels are uncertain. Furthermore, some individuals taking rather large doses of antioxidants still have evidence of significant free radical production. The present invention provides the benefits of antioxidants through electrical stimulation that increases endogenous antioxidant levels without the need for exogenous supplements.

This invention pertains to a method for enhancing antioxidant levels in human beings without administration of exogenous antioxidants through diet or supplements.
Oxidative stress is thought to be involved in the aging process in aerobic organisms and to play a role in the pathogenesis of several disease states, including Alzheimer""s disease, myocardial infarction, atherosclerosis, Parkinson disease, autoimmune diseases, radiation injury, emphysema, sunburn, glomerular disorders, schizophrenia, sickle cell disease, leukemia, osteoporosis, infertility, cancer, retinopathy, and noise-related hearing impairment. Oxidative stress is the result of free radicals, such as the hydroxyl radical, reacting with biological macromolecules, such as lipids, proteins, nucleic acids and carbohydrates. The initial reaction generates a second radical, which in turn can react with a second macromolecule to continue the chain reaction. In the process of reacting, a free radical can modify protein or DNA structures, disrupt individual nucleotide bases, and thereby cause effects such as single-strand breaks and cross-linking in nucleic acids. Free radical-induced oxidative stress has been associated with a number of major cardiovascular disease risk factors. See xe2x80x9cReactive Oxygen Species (ROS)xe2x80x9d (first printed in R and D Systems"" 1997 Catalog), available at http://www.rndsystems.com/asp/g_sitebuilder.asp?bodyId=222.
A current theory holds that free radical-induced oxidative stress is a major factor in the long-term tissue degradation associated with aging. This free radical theory proposes that aging is the cumulative result of oxidative damage to the cells and tissues of the body that arises primarily as a result of aerobic metabolism. Several lines of evidence have been used to support this hypothesis including the claims that: (1) Variation in species life span is correlated with metabolic rate and protective antioxidant activity; (2) enhanced expression of antioxidative enzymes in experimental animals can produce a significant increase in longevity; (3) cellular levels of free radical damage increases with age; and (4) reduced calorie intake leads to a decline in the production of free radical and an increase in life span. The free radical theory may also be used to explain many of the structural features that develop with aging including the lipid peroxidation of membranes, formation of age pigments, cross-linkage of proteins, DNA damage and decline of mitochondrial function. Wickens, A. P., xe2x80x9cAgeing and the free radical theory,xe2x80x9d Respir. Physiol., Vol. 128(3), pp. 379-91 (2001).
Free radicals only occur in trace quantities in biological tissues and are extremely reactive. Because of the difficulty of directly measuring free radicals in vivo, measurements can be made using biomarkers, for example, an assay of antioxidant vitamins and free radical scavengers. Therefore, oxidative stress has been mainly observed through such indirect biomarkers of free radical-induced damage. In aerobic organisms, oxidative damages to tissues and organs is prevented by a network of defenses which include antioxidant and repairing enzymes, as well as small molecules with scavenging ability, such as antioxidant vitamins. For these reasons, the assay of antioxidant vitamins and of small molecular free radical scavengers in biological milieus may be used, if appropriately performed, to quantify the defense status against oxidative damage and to provide an indirect estimate of free radical production in aging humans. Polidori, M. C., et al., xe2x80x9cPeripheral non-enzymatic antioxidant changes with human aging: a selective status report,xe2x80x9d Biogerontology, Vol. 2(2), pp. 99-104 (2001).
Malondialdehyde (MDA) levels both in blood and urine have been one of the most widely used free radical markers. Measurement of MDA excretion in the urine became available in 1964. MDA is the end product of lipid peroxidation, and this urinary calorimetric assay represents by far the simplest approach to measurement of free radical activity. Furthermore, this colorimetric assay has been highly statistically significantly correlated with the fluorometric approach.
Mammalian cells possess elaborate defense mechanisms to detoxify radicals. Radical-scavenging antioxidants (e.g., vitamin E) interrupt the chain by capturing the radical; the vitamin E radical is relatively stable, and it can be enzymatically converted to its non-radical form. Excessive amounts of cellular oxidants, which animal cells constantly produce, can induce oxidative damage. Cellular antioxidants provide a defense against the damaging effects of the cellular oxidants. However, in moderate concentrations, cellular oxidants are necessary for a number of protective reactions which eliminate cancerous and other life-threatening cells, such as anti-microbial phagocytosis and apoptosis. Excess antioxidants could inhibit the protective anti-cancer function that the apoptosis process provides. Abundant antioxidants might suppress these protective functions, particularly in people with a low innate baseline level of cellular oxidants. Salganik, R. I., xe2x80x9cThe benefits and hazards of antioxidants: controlling apoptosis and other protective mechanisms in cancer patients and the human population,xe2x80x9d J. Am. Coll. Nutr., Vol. 20(5 Suppl.), pp. 464S-472S (2001).
Conventional antioxidant supplements comprise, for example, vitamin C, vitamin E, beta-carotene, or other forms such as red ginseng or DHEAs, for example. Given that antioxidant supplements can actually be harmful in high doses to patients who have low levels of baseline cellular oxidants, safe antioxidant supplement use requires an accurate dosage level corresponding to each patient""s needs. Each patient""s baseline needs would have to be determined periodically because it is also clear that the optimal dosage of antioxidant supplements probably varies over time with each patient. Meagher, E., et al., xe2x80x9cAntioxidant therapy and atherosclerosis: animal and human studies,xe2x80x9d Trends Cardiovasc. Med., Vol. 11 (3-4), pp. 162-5 (2001).
In healthy individuals, a delicate balance exists between the production of free radicals and the production of antioxidants. Free radicals are produced in the body as byproducts of normal metabolism and as a result of exposure to radiation and some environmental pollutants. They are normally neutralized by the body""s production of antioxidant enzymes (super oxide dismutase, catalase, and glutathione peroxidase) and the nutrient-derived antioxidant small molecules (Vitamin E, Vitamin C, carotene, flavonoids, glutathione, uric acid, and taurine). In some pathological conditions, the natural balance can be upset by oxidative stress in the presence of certain diseases, such as diabetes. The oxidative stress can cause a reduction in the body""s normal production of antioxidants. To prevent deterioration of antioxidant levels, it is conventionally recommended to consume adequate amounts of antioxidant-rich foods, e.g., fruits and vegetables, and also to take supplements as necessary. Sardesai, V. M., xe2x80x9cRole of antioxidants in health maintenance,xe2x80x9d Nutr. of Clin. Pract., Vol. 10(1), pp. 19-25 (1995).
Despite the extensive research in the use of antioxidants, there is not a clear-cut consensus that these antioxidants are totally successful in reducing free radicals. Sacheck, J. M., et al., xe2x80x9cRole of Vitamin E and Oxidative Stress in Exercise,xe2x80x9d Nutrition, Vol. 27(10), pp. 809-14 (2001), Meagher, E., et al., xe2x80x9cAntioxidant Therapy and Atherosclerosis: Animal and Human Studies,xe2x80x9d Trends Cardiovasc. Med., Vol. 11(3-4), pp. 162-5 (2001). Although cancer tissue has significant decreases in glutathione, vitamin C, and vitamin E, there is no evidence that taking the supplements actually prevents cancer. Skrzydlewska, E., et al., xe2x80x9cAntioxidant Status and Lipid Peroxidation in Colorectal Cancer,xe2x80x9d Toxicol. Environ. Health A., Vol. 64(3), pp. 213-22 (2001). On the other hand, there is considerable evidence that the antioxidants found in natural sources, such as vegetables and fruits, do have a beneficial effect. Trichopoulou, A., et al., xe2x80x9cGuidelines for the Intake of Vegetables and Fruit: The Mediterranean Approach,xe2x80x9d Int. J. Vitam. Nutr. Res., Vol. 71(3), pp. 149-53 (2001). Despite the lack of great clinical significance in the use of antioxidants, there is a great argument for the use of micronutrient antioxidants as a standard in many diseases, including cancer and Type 2 diabetes. It is also of some interest that the antioxidants themselves apparently do not ordinarily cross the blood brain barrier, a significant problem in reducing the known negative effects of free radicals in many degenerative central nervous system diseases, such as Alzheimer""s. Blass, J. P., xe2x80x9cBrain Metabolism and Brain Disease: Is Metabolic Deficiency the Proximate Cause of Alzheimer Dementia?xe2x80x9d J. Neurosci. Res., Vol. 66(5), pp. 851-56 (2001). Finally, an effective antioxidant supplement regimen can be expensive to maintain.
Other than antioxidants, there is only one known non-antioxidant technique for reducing free radicals. That is, 6 degrees head down bed rest; however, that can require as much as 17 days of simulated weightlessness. Furthermore, bed rest and the corresponding inactivity have also been linked to increased free radical levels. Peng, Y., et al., xe2x80x9cEffects of Hyposi and Qigong on Urine Malondialdehyde, Superoxide Dismutase and Circulating Endothelial Cell in Humans During Simulated Weightlessness,xe2x80x9d Space Med. Eng. (Beijing), Vol. 11 (2), pp. 136-8 (1998); Pawlak, W., et al., xe2x80x9cEffect of Long Term Bed Rest in Men on Enzymatic Antioxidative Defence and Lipid Peroxidation in Erythrocytes,xe2x80x9d J. Gravit. Physiol., Vol. 5(1), pp. 163-4 (1998).
It has been disclosed that treating a patient with electrical stimulation at acupuncture points known as the xe2x80x9cRing of Air,xe2x80x9d can endogenously increase serum neurotensin levels in living human beings. See U.S. Pat. No. 6,233,489. It has also been disclosed that treating a patient with electrical stimulation at acupuncture points known as the xe2x80x9cRing of Firexe2x80x9d can increase serum dehydroepiandrosterone (DHEA) levels. See U.S. Pat. No. 5,109,847. Until now, however, there has been no known method of reducing free radical levels in a living human being in a manner similar to the xe2x80x9cRing of Airxe2x80x9d or xe2x80x9cRing of Firexe2x80x9d electrical stimulation.
The present invention provides a method for enhancing or restoring antioxidant levels in a living human being. Because antioxidants are naturally occurring in the human body, in accordance with the present invention endogenous production of antioxidants may be stimulated without requiring the use of exogenous dietary supplements or pharmaceutical preparations containing antioxidants or antioxidant analogs.
Antioxidants levels in human beings may be raised without the use of dietary supplements or pharmaceuticals by applying electrical stimulation to specific epidermal points of the individual""s body for a period of time, preferably daily. The electrical stimulation is preferably applied to specific locations on the individual""s body which correspond to 13 well-known acupuncture points known as the xe2x80x9cRing of Crystal.xe2x80x9d The electrical stimulation can be applied to these acupuncture points over a number of weeks to achieve a significant increase in antioxidant levels and a corresponding decrease in free radical activity within the patient. Preferably, electrical stimulation is applied for a minimum period of 2 to 4 weeks.
Electrical stimulation of the Ring of Crystal acupuncture points on the human body, in accordance with the present invention, has been shown to be highly efficacious among 80 percent of subjects tested in reducing free radicals, and it does not appear to risk potentially excessive antioxidants levels that may be produced by increased dosages of exogenous antioxidant supplements.
Further objects, features and advantages of the invention will be apparent from the following detailed description taken in conjunction with the accompanying drawings.

Electrical stimulation to reduce free radical levels


A blower housing of novel two-piece construction is comprised of first and second housing parts of stamped or drawn sheet metal that are attached together. The two-piece construction provides the housing with two interior portions separated by an interior wall. The interior wall has an opening that is spaced from the aligned exhaust opening of the heater and the output opening of the housing. This creates a winding exhaust gas flow path through the blower housing. The interior wall is also provided with a recessed cavity that receives a portion of a fan rotated by a motor supported by the blower housing. Positioning of at least a portion of the fan in the cavity reduces the overall height dimension of the blower housing and facilitates the retrofitting of the blower housing between an existing exhaust opening of a heater and an axially aligned flue pipe.

1. Field of the Invention
The present invention pertains to a heater blower apparatus that is primarily intended for use as a non-dilution water heater blower. The apparatus is designed to be retrofit to an existing water heater between the axially aligned heater exhaust opening and a flue pipe.
2. Description of the Related Art
In the basic construction of a water heater, a fuel such as gas is burned in a combustion chamber of the water heater to heat water passed through the water heater. The water typically travels through a series of coils in the water heater. Combustion of the fuel in the combustion chamber produces hot combustion exhaust gas that passes through the series of coils and heats the water passing through the coils. The combustion exhaust gas then exits the water heater through an exhaust opening of the water heater and then passes through a flue pipe that conducts the gas out of the building containing the water heater.
Many prior art water heaters are connected to a flue pipe or chimney where only the draft effect of the flue pipe or chimney moves the exhaust gas up through the flue pipe or chimney. Because only the difference in temperature and pressure between the hot exhaust gas inside the water heater and the ambient air outside the water heater would cause the gas to move upwardly through the flue pipe or chimney, prior art water heaters were designed to avoid restricting the flow of the exhaust gas upwardly through the water heater to ensure that the gas would exit the water heater through the flue pipe or chimney. This limited the number of coils that could be positioned inside the water heater so as not to overly restrict the flow of the exhaust gas through the water heater. This in turn reduced the efficiency of the water heater.
To increase efficiency, water heaters have been designed where the hot gas of combustion is drawn through an increased number of coils of the water heater to provide an increased amount of heat transfer from the heat of the gas to the water passing through the coils. A greater number of coils enables a greater amount of heat transfer. However, this also required that the water heater be constructed with a blower apparatus that would draw the combustion gas through the coils of the water heater and to the flue pipe exhausting the gas.
The addition of a blower apparatus to a water heater increased the overall cost of the water heater. In addition, because the blower apparatus would draw the exhaust gas quickly through the water heater and into the blower apparatus, the increased temperature of the exhaust gas drawn into the blower apparatus often required that the blower apparatus mix ambient dilution air with the hot exhaust gas to cool the gas. The need to draw dilution air into the blower apparatus to cool the exhaust gas often required that the blower apparatus have a more complicated blower housing design and a more powerful motor for the fan of the apparatus. The more complicated blower housing design often increased the cost of manufacturing the blower apparatus, detracting from the energy savings of the dilution blower apparatus. The energy used by the more powerful motor also would negate some of the energy savings realized by increasing the heat transfer between the combustion gas and the coils of the water heater.

Non-dilution blower apparatus for high efficiency water heater


A method comprises: acquiring, for a number nSOP of varied State-Of-Polarization analysis conditions of the input optical signal, nSOP polarization-analyzed optical spectrum traces; mathematically discriminating said signal contribution from said noise contribution within said optical signal bandwidth using said polarization-analyzed optical spectrum traces, said mathematically discriminating comprising: obtaining a differential polarization response that is related to the optical spectrum of said signal contribution by a constant of proportionality; estimating the constant of proportionality of a differential polarization response to the optical spectrum of said signal contribution; estimating the optical spectrum of said noise contribution from said input optical signal, within said optical signal bandwidth using said constant of proportionality and said differential polarization response; and determining said in-band noise parameter on said input optical signal from the mathematically discriminated noise contribution.

The Optical Signal-to-Noise Ratio (OSNR) is a direct measure of the quality of signal carried by an optical telecommunication link. Under normal and proper operating conditions, the OSNR of an optical communication link is typically high, often in excess of 15 dB or 20 dB, or even greater. The dominant component of the noise in an optical communication link is typically unpolarized Amplified Spontaneous Emission (ASE), which is a broadband noise source contributed by the optical amplifiers in the link. In general, the ASE may be considered to be spectrally flat across the small wavelength range spanning the full signal spectral width, provided that there is no spectral filtering in the vicinity of the signal.
The IEC 61280-2-9 Fiber-optic communication subsystem test procedures—Part 2-9 standards (ed. 1.0 b:2002) provides a standard method for determining OSNR in Dense Wavelength Division Multiplexing (DWDM) networks. This method is based on the assumption that the interchannel noise level is representative of the noise level at the signal peak position. The method interpolates the power level of the noise outside the signal bandwidth to evaluate the in-band noise in the signal bandwidth. Increased modulation rates, which enlarge the signal bandwidth, and increased channel density, reduce the interchannel width; therefore resulting in severe spectral characteristics requirements for the optical spectrum analyzers used to perform the measurement. The procedures described in the standards are able to cope with these difficulties when the noise level of adjacent peaks is mostly continuous. For example, the standards propose a two-scan procedure to first measure a broad modulated peak with a larger resolution bandwidth to capture the entire signal peak and then determine the noise using a narrow resolution bandwidth to minimize the contributions of the main and adjacent peaks on the interchannel noise level. Alternatively, commercial Optical Spectrum Analyzers (OSA) (such as EXFO's FTB-5240, in its versions available before 2007) implement a related procedure by performing an integrated peak calculation and fine noise determination in a single scan.
However, to strictly comply with the standards recommendation, the noise level should be determined at the mid-channel spacing between peaks. In the case where noise is spectrally filtered with the signal peak, for instance, after passing through multiplexers or demultiplexers—such as Reconfigurable Optical Add Drop Multiplexers (ROADM)—the mid-spacing noise level is no longer representative of the in-band noise level, which is the relevant parameter for the OSNR determination. The interpolation of the interchannel noise level then becomes unreliable. This can be mitigated by relying on a very sharp spectral response of the OSA filter and adaptive processing to determine the noise level at the shoulders where the noise meets the base of a signal profile within the channel bandwidth. However, increased modulation rates combined with narrow filtering of multiplexers and demultiplexers is making it increasingly difficult to achieve a reliable measurement of the noise level within the channel bandwidth.
Active polarization-nulling (see J. H. Lee et al, "OSNR Monitoring Technique Using Polarization-Nulling Method", IEEE Photonics Technology Letters, Vol. 13, No. 1, January 2001) provides an alternative to a direct analysis of the optical spectrum. This method uses the fact that the signal peak is generally polarized while the noise is generally unpolarized. Using a polarization controller cascaded with a polarizer (the latter serving as an analyzer), it is possible to actively control the polarization of the input signal in order to find a condition where the signal peak is maximally suppressed by the polarizer. An optical spectrum trace is acquired while the signal peak is suppressed and reveals the in-band noise within the optical channel bandwidth. The noise level within the optical channel bandwidth can be determined using the acquired optical spectrum trace.
Variants to the active polarization-nulling method are described in U.S. Pat. No. 7,106,443 to Wein et al.; in Sköld et al., "PMD-insensitive DOP-based OSNR monitoring by spectral SOP measurements", Paper OThH3, Optical Fiber Communications Conference, Anaheim, USA, March 2005); and in U.S. Pat. No. 7,756,369 to Rudolph et al.
The active polarization-nulling method and its variants all require that the polarized signal peak be suppressed at or very close to zero. In practice, this requires a degree of extinction of the signal peak which is at least 10 dB greater than the highest possible OSNR to be measured. For example, for measuring an OSNR of 25 dB within an accuracy of 0.5 dB, a 38-dB extinction is required. This high degree of extinction imposes constraints on the instrumental noise floor that normally is often limited by the electronics, quality of the polarization-diversity optics, etc., which, in order to be satisfactorily overcome, requires increasing the inherent cost of the instrument. Notwithstanding the aforementioned instrumental constraints, attainment of such a high extinction ratio also requires either an excellent coverage of the States-Of-Polarization (SOPs) on the Poincaré sphere, i.e. the generation of a very large number of SOPs or the use of a full "high-end", i.e. very accurately calibrated, and hence costly polarimetric OSA.
It is noted however that the limiting noise source in most optically-filtered long-haul optical networks is the signal-ASE beat noise, in which the signal and the ASE interfere at baseband frequencies within the electronic detection bandwidth. In typical optical communications systems employing optical amplifiers, signal-ASE beat noise is the limiting noise term for optical performance, and can be directly related to the Bit Error Rate (BER) of the optical communication channel. Thus, estimation of the in-band OSNR provides an indicative measure of the system performance. However, new systems are currently being developed and deployed which exploit multi-bit-per-symbol advanced modulation formats to transmit more than 100 Gbit/s, with symbol rates of 27 GBaud and higher. Not only are the associated optical spectra of the modulated signals much wider than previous (generally on-off-keying) 10 Gb/s systems, but the spectral profiles are often more complicated, and not necessarily "sharply peaked" at the center. Hence, accurate signal-ASE beat noise estimations may require a convolution of the superposed (or "underlying", a less rigorous but widely employed terminology) optical noise spectral trace with the signal spectral trace. In tightly filtered systems, this underlying noise is itself often filtered over a significant portion of the channel bandwidth, near the filter edges. Accordingly, OSNR of such systems can not be determined reliably based on an estimation of the underlying in-band noise assuming a flat optical noise spectral trace.
There is thus a need for reliably determining the optical noise spectral trace underlying the optical signal peak. In particular, there is a need of methodology that is applicable in the case of DWDM networks, where individual channels may carry respective signals that have traversed different optical links and hence have different underlying noise properties.

In-band optical noise measurement using differential polarization response


A system and method for e-mail screening to prevent the spread of viruses and to compensate users for viewing unsolicited e-mails. Users have all incoming e-mails redirected to a e-mail screening site. When the user registers with the server of the present invention, the user designates a password to the screening site and inform email senders of the password. When email comes to the user, it is redirected to the server site. IF a password is present in the e-mail it is sent directly back to the user. If there is no password present, the email is scanned and the sender is notified that, for a fee, the email can be forwarded to the user. If the sender pays the fee to the server site, the scanned email is forwarded and the fee is then shared with the user.

It is frequently a problem that email received by an individual may contain a virus which is either specifically intended to infect the machine or is inadvertently attached by a known user to email being sent to a recipient. In either case, the end result is the recipient having the virus infect the system. Obviously, this can lead to disastrous results.
Email processing for various purposes has been the subject of invention. For example:
U.S. Pat. No. 5,889,943 to Ji, et al. describes a method and apparatus for virus detection for e-mail files. This patent describes a network of nodes separating servers that perform processing functions. Particularly, the system architecture allows e-mail messages to be sent to a separate server in order to be scanned. It does not deal with sorting of messages to be forwarded or otherwise identifying desired from undesired email.
U.S. Pat. No. 5,623,600 to Ji, et al. is related to the above-mentioned patent ('943). This patent describes a system for scanning files on a computer network for viruses. More specifically, the inventions include two methods that involve transferring email messages to a separate node in order for the virus scan to be performed. One embodiment provides detection from a gateway node for files sent to or from a network. Each method describes the scanning function as being performed by a separate server.
U.S. Pat. No. 5,832,208 to Chen, et al. describes a software program that scans for and removes viruses from e-mail messages, including attached files. One embodiment shows software used at the mail server of a Local Area Network (LAN) and operates within the mail system. The patent discusses applications for the program in a wide variety of computer architecture arrangements, including network operating systems and virus detection programs. However, this method is primarily based at the e-mail server. It does not deal with the sorting of email or revenue generation.
U.S. Pat. No. 5,901,228 to Crawford describes a system that allows on-line customers to directly access storage capability on a host system. One feature of the system is that the customer may purchase virus detection capability. However, several of the capabilities purchased, including virus detection require some virus-detection processing to be done at the customer's computer.
Anti-viral services are particularly described as being executable from either a virtual disk or copied onto the customer's hard drive.
The system described does operate when the user is off-line. The replica computer can act off-line and perform functions when the customer is not connected to the system.
U.S. Pat. No. 5,771,354 to Crawford is related to the above-mentioned patent ('228). This patent describes an on-line system where customers use the host system to perform storage and processing functions that were previously done on the customer's system. Specifically, the customer connects to the provider, pays a fee, and obtains the service. When the customer first contacts the provider, he must establish an identifier and password. Subsequently, the customer's access is permitted with entering the proper identifier and password. This service allows access by recipients of emails. It does not deal with the sender of email in any way.
U.S. Pat. No. 5,864,683 to Boebert, et al. describes a computer system that protects a private and secure system from infiltration while a secure user is accessing a wide-area access system. One embodiment describes a system where the secure user connection is processed by a secure server. The secure server isolates the private and wide-are access systems. The secure server is described as a non-distinguishing server that automatically reroutes information packets with a certain type of header for "off-line" inspection
As seen in several of the patents discussed above, screening e-mail messages for virus infection via an off-line server is well known. While some patents address the purchase of a service by a recipient to screen e-mail for viruses, recipients are charged for performing the service of screening his or her e-mail for viruses.
These patents do not address connections that a user will make with third parties. None of the patents consider any way of recouping costs from third parties (senders of emails).
No other reference in the search describes a virus-screening system application that allows third party users of the customer's system to be charged when communicating with any user from the LAN.
What would be truly useful would be a system that allows emails and attachments to be screened, and which provides notification to both the user that such email has arrived and its potential subject matter, that allows a user to have email selectively screened, that provides notification to senders that a screening activity has taken place, and that makes a nominal charge to the sender for delivery of the scanned email.


In a first aspect, a loadport is provided. The loadport has a plate adapted to couple to a door of a substrate carrier to open the substrate carrier wherein the plate includes a first opening adapted to couple to a first port in the door of the substrate carrier on a first side of the plate and to couple to a gas source on a second side of the plate, and wherein the loadport is adapted to allow a flow of gas into the substrate carrier via the first opening in the plate. Methods of purging substrate carriers are provided, as are numerous other aspects.

Manufacturing of semiconductor devices typically involves performing a sequence of procedures with respect to a substrate such as a silicon substrate, a glass plate, etc. (Such substrates may also be referred to as wafers, whether patterned or unpatterned.) These steps may include polishing, deposition, etching, photolithography, heat treatment, and so forth. Usually a number of different processing steps may be performed in a single processing system or "tool" which includes a plurality of processing chambers. However, it is generally the case that other processes are required to be performed at other processing locations within a fabrication facility, and it is accordingly necessary that substrates be transported within the fabrication facility from one processing location to another. Depending upon the type of semiconductor device to be manufactured, there may be a relatively large number of processing steps required to be performed at many different processing locations within the fabrication facility.
It is conventional to transport substrates from one processing location to another within substrate carriers such as sealed pods, cassettes, containers and so forth. To prevent damage to substrates transported within substrate carriers, care should be taken to ensure that substrates are not contaminated during transport with the substrate carriers. Methods and apparatus for reducing the contamination of substrates within a substrate carrier are desired.

Methods and loadport apparatus for purging a substrate carrier


An improved method for defect detection with systems using magnetostrictive sensor techniques. The improved method involves exciting the magnetostrictive sensor transmitter by using a relatively broadband signal instead of a narrow band signal typically employed in existing procedures in order to avoid signal dispersion effects. The signal detected by the magnetostrictive sensor receiver is amplified with an equally broadband signal amplifier. The amplified signal is transformed using a time-frequency transformation technique such as a short-time Fourier transform. Finally, the signal characteristics associated with defects and anomalies of interest are distinguished from extraneous signal components associated with known wave propagation characteristics. The process of distinguishing defects is accomplished by identifying patterns in the transformed data that are specifically oriented with respect to the frequency axis for the plotted signal data. These identified patterns correspond to signals from either defects or from known geometric features in the pipe such as welds or junctions. The method takes advantage of a priori knowledge of detected signal characteristics associated with other wave modes (such as flexural waves) and sensor excitation as well the effects caused by liquid induced dispersion.

1. Field of the Invention
The present invention relates generally to methods for the Non-Destructive Evaluation (NDE) of pipes and tubes using magnetostrictive sensor technologies. The present invention relates more specifically to an improved method for detecting defects in the signal analysis process associated with the use of magnetostrictive sensor technologies for the inspection of pipes and tubes.
2. Description of the Related Art
Magnetostrictive sensor technologies have been used successfully for a period of time with the inspection of pipes and tubes in processing plants such as refineries, chemical plants, steam process plants and the like. Examples of the use of magnetostrictive sensors, and the various analytical techniques associated therewith, are disclosed in U.S. Pat. Nos. 5,456,113 and 5,457,994, each entitled Non-Destructive Evaluation of Steel Cables and Ropes Using Magnetostrictively Induced Ultrasonic Waves and Magnetostrictively Detected Acoustic Emissions, as well as U.S. Pat. No. 5,581,037 entitled Non-Destructive Evaluation of Pipes and Tubes Using Magnetostrictive Sensors, all of which are commonly owned by the assignee of the present invention, Southwest Research Institute.
The techniques associated with such NDE inspections of pipes, tubes, cables and the like typically involve generating longitudinal waves along the length of the pipe or tube and analyzing signals that are reflected from defects and anomalies within the pipe or tube. One of the many advantages of this technique is the ability to detect defects by sensing the reflected signal at the same physical location at which the interrogating signal waves are generated.
Because mechanical waves generated by magnetostrictive sensors can propagate a long distance along a structure under inspection the techniques are capable of inspecting very long or large segments, typically more than a hundred feet under favorable conditions, of pipe very rapidly. These techniques also provide a complete volumetric inspection of a long section of pipe with minimum ancillary activity such as surface preparation, scaffolding or insulation removal. These magnetostrictive sensor methods therefore offer a very efficient and comprehensive mechanism for pipe and tube inspection.
In general, the longitudinal wave modes utilized in the above referenced techniques for inspection are dispersive in nature. This means that the velocity of the mechanical wave propagation varies with the wave frequency. FIG. 1 provides a illustrative example of the dispersion curves for the first two longitudinal wave modes, L(0,1) and L(0,2), which are typically used with the above referenced magnetostrictive sensor techniques. To simplify the detection of defects within the reflected signal pattern, the techniques described above utilize the waves in the frequency region where the dispersion curve is relatively flat (V.sub.o and V.sub.p) and avoid those regions (V.sub.o /2.pi.b and KV.sub.p /2.pi.b) where the dispersion curve changes rapidly with frequency. In order to confine the bandwidth of the wave pulse within the desired frequency range, and thus avoid excessive dispersion effects, a relatively narrow band excitation signal is used for transmitting the interrogating waves into the pipe structure. A tonal burst consisting of several cycles of sinusoidal wave at a specific wave frequency have been typically employed for this purpose. The effectiveness of magnetostrictive sensor techniques along these lines has been well proven in operating processing plants.
It has been recognized, however, that positive discrimination and identification of defect signals within the overall detected signal can sometimes be difficult due to the presence of extraneous signals not associated with defects and anomalies. These extraneous signals include those of other wave modes (mostly flexural) that might be produced in the pipe wall due to non-symmetric material properties and sensor excitation. In addition, for situations where the pipe or tube is liquid filled, extraneous signals can be caused by liquid induced dispersion effects. These extraneous signals may be confused as defect reflections or may mask or radically alter defect signals present in the detected signals.
Examples of previous attempts in the prior art to improve the defect detectability of NDE sensors include the following patents:
U.S. Pat. No. 5,612,495 issued to Shimada et al. on Mar. 18, 1997, entitled Non-Destructive Examination Device, describes a system that uses magnetostrictive transmitters and response sensors to carry out the non-destructive evaluation of a material. The system anticipates the use of a resonant frequency for the interrogating signal. The signal processing methods are described as potentially including a high speed Fourier transformation process or an integral process. No specific characterization or selection of the best or most appropriate signal processing method is made.
U.S. Pat. No. 5,526,689 issued to Coulter et al. on Jun. 18, 1996, entitled Acoustic Emission for Detection of Corrosion Under Insulation, describes a method and apparatus for detecting the presence of surface corrosion under insulation on a pipe structure. This patent anticipates the use of a broadband of acoustic waves to interrogate the structure. The sound waves are detected by piezoelectric sensors and converted to electrical signals for processing. The signal analysis method in Coulter et al. involves producing RMS voltage signals indicative of the detected sound waves and comparing the RMS voltage signals to standard signals obtained from uncorroded piping. The analysis involves a strict amplitude comparison to distinguish the signal component from the defect.
U.S. Pat. No. 5,195,046 issued to Gerardi et al. on Mar. 16, 1993, entitled Method and Apparatus for Structural Integrity Monitoring, describes a piezoelectric transducer based system designed for the detection, monitoring, and analysis of such things as aircraft structures. The system utilizes vibration signatures and recognizes changes in the vibration signatures as indicative of faults, cracks, deteriorations, etc. Various pattern recognition techniques are utilized. Data acquisition is accomplished using piezoelectric sensors and is digitized before being converted to the frequency domain via a fast Fourier transform. Time and/or frequency domain signatures are used in the signature pattern analysis. The patent lists 25 illustrative features (column 11) that include both time and frequency domain parameters as providing the basis for pattern recognition.
U.S. Pat. No. 5,665,913 issued to Chung on Sep. 9, 1997, entitled Method and Apparatus for Evaluation and Inspection of Composite-Repaired Structures, describes a system and method for NDE of composite-repaired structures wherein the signal transmitters and sensors are piezoelectric based devices. Analysis is carried out by comparing an output signal to a baseline reference signal generated at the time of composite repair. The signal processor involved in Chung includes an isolation filter, an amplifier, and a frequency domain integrator. The system anticipates the use of either a single frequency for interrogating the material or a range of frequencies.
U.S. Pat. No. 5,469,060 issued to Meyerand on Nov. 21, 1995 entitled Time Encoded Magnetic Resonance Imaging, describes a system that utilizes a separate set of signal transducers and applies a resonant frequency pulse to the material under investigation. The RF signals received as a function of time are converted to a set of frequency domain functions at specific times relating to specific strips in the image being generated. The frequency domain functions in the form of strips are combined sequentially to form the entire time frequency domain function image.
U.S. Pat. No. 5,719,791 issued to Neumeier et al. on Feb. 17, 1998, entitled Methods, Apparatus and Systems for Real Time Identification and Control of Modes of Oscillation, describes various methods for signal identification within a noisy background. The Neumeier et al. patent describes a system for controlling vibrations and oscillations with real time detection and compensation through an actuator. Various time frequency functions are applied to the signal for analysis.
U.S. Pat. No. 5,574,639 issued to Qian et al. on Nov. 12, 1996, entitled System and Method for Constructing Filters for Detecting Signals Whose Frequency Content Varies With Time, is generally directed to a signal analysis method intended to reliably detect the presence of signals of interest, especially those whose frequency content varies with time. The Qian et al. invention is directed to the development and use of time templates designed to match the received signal of interest. The patent describes its application as including any situation where a signal travels through media and wherein the media transforms or disperses the signal into a signal whose frequency content varies with time. The patent applies what is referred to as the Gabor Spectrogram to a computer representation of the signals in the joint time-frequency domain for the purpose for instantaneous frequency estimation. The patent distinguishes STFT as not being the ideal representation for tracking the parameters of concern.
U.S. Pat. No. 5,439,157 issued to Geier et al. on Aug. 8, 1995, entitled Automated Butt Weld Inspection System, describes an electromagnetic acoustic transducer (EMAT) based system that produces an ultrasonic shear wave in a material containing welds and the like. A second EMAT receives the reflected shear wave.
None of the above described methods and systems, however, have been able to adequately distinguish signal characteristics that derive from extraneous features of no interest from those signal components that derive from the types of defects and anomalies of interest in a damage, deterioration, or corrosion study. The signal analysis techniques utilized thus far are generally incapable of distinguishing a time, frequency and amplitude signal component associated with a defect of interest from similar time, frequency and amplitude signal components associated with geometric and/or otherwise non-relevant causes.
It would be desirable to have an NDE system for pipe and/or tube inspection that utilizes magnetostrictive sensor techniques and is capable of analyzing a detected signal in a manner that permits the discrimination of extraneous signal components not representative of defects or anomalies of interest. It would be desirable if such a system could be automated to the extent that rapid discrimination of such signal components not representative of defects or anomalies of interest, would provide an accurate and rapid identification of the location and nature of defects and anomalies of interest.

Method for improving defect detectability with magnetostrictive sensors for piping inspection


This invention relates to the use of hydroxybutyrate and poly hydroxybutyrate as components of animal feed or feed additives, as well as to compositions, feed additives and feed containing them. The inventors surprisingly found that hydroxybutyrate and poly-hydroxybutyrate, preferably 3-hydroxybutyrate and poly-3-hydroxybutyrate, have a great potential for use in animal feed for modulation of the gut flora. More precisely, it has been found that poly-3-hydroxybutyrate or a microbial strain capable for producing poly-3-hydroxybutyrate can be used as a potential growth promoter or gut flora modulator by releasing SCFA, preferably 3-hydroxy butyric acid, in the gut micro flora. Further, the inventors found that 3-hydroxybutyrate and poly-3-hydroxybutyrate have a great potential for suppressing or inhibiting pathogenic bacteria in the gastro intestinal tract, e.g. have a antimicrobial activity against strains of Vibrio, E. coli and Salmonella.

This invention relates to the use of hydroxybutyrate and poly-hydroxybutyrate as components of animal feed or drinking water or feed or drinking water additives, as well as to compositions, feed additives, drinking water and feed containing them.
The term feed or feed composition means any compound, preparation, mixture, or composition suitable for, or intended for intake by an animal.
More particular, the present invention relates to the use of 3-hydroxybutyrate (HB) or a salt, ester, or combination of HB, a HB salt and a HB ester, or poly-3-hydroxybutyrate (PHB) or a salt, ester, or combination of PHB, a PHB salt and a PHB ester as active ingredients of nutraceutical compositions for animals.
The term "nutraceutical" as used herein denotes a usefulness in both the nutritional and pharmaceutical field of application. Thus, the nutraceutical compositions can find use as a complete animal feed (diet), as supplement to animal feed, and as pharmaceutical formulations for enteral or parenteral application which may be solid formulations, or liquid formulations.
The term animal includes all animals including human. Examples of animals are non-ruminants, and ruminants. Ruminant animals include, for example, animals such as sheep, goat, and cattle, e.g. cow such as beef cattle and dairy cows. In a particular embodiment, the animal is a non-ruminant animal. Non-ruminant animals include pet animals, e.g. horses, cats and dogs; mono-gastric animals, e.g. pig or swine (including, but not limited to, piglets, growing pigs, and sows); poultry such as turkeys, ducks and chickens (including but not limited to broiler chicks, layers); fish (including but not limited to salmon, trout, tilapia, catfish and carp); and crustaceans (including but not limited to shrimp and prawn).
In farm animals suppression of enteric diseases on one hand and growth promotion on the other hand have been achieved by the inclusion of antibiotics and/or chemotherapeutics into the diets.
On the one hand, butyric acid is known as a "soft" antimicrobial which shows a "prebiotic" effect when treated to animals. Butyric acid has a strong positive effect on the enterocytes and colonocytes proliferation and maturation. Currently butyric acid is added (mostly together with antibiotics) to animal feed as prebioticum after it is synthesized, neutralized with CaO and worked up with silicate. But one of the big disadvantages of using butyric acid in animal nutrition is that the current butyric acid products are sticky and smell very bad.
On the other hand, in recent years, considerable attention has been also paid to short chain fatty acids (SCFAs) as an alternative to traditional growth promoters. For example European patent application 1′661′574 discloses a composition comprising polymers of short to medium chain hydroxy fatty acids, hereinafter also called "Polyhydroxyalkanoates (PHAs)", which are used for delivering the hydroxy fatty acid or an oligomer thereof to the large intestine. In case the composition is administrated orally, the composition will be delivered to the large intestine, without being degraded in the stomach or short intestine, but being degraded by the large intestinal bacterial flora resulting in the release of the short to medium chain fatty acids or oligomers thereof. EP 1′661′574 further discloses that the released short to medium chain fatty acids or oligomers thereof have useful physiological activities and are effective for treating or preventing inflammatory diseases or cancer in the large intestine.

Hydroxybutyrate and poly-hydroxybutyrate as components of animal feed or feed additives


The present invention relates to a method and apparatus for increasing the delivery rate of an androgen transdermal therapeutic system through the skin. An androgen transdermal therapeutic system can be applied to a patient""s skin for delivery of the androgen. A temperature modification apparatus which is capable of generating controlled heat is applied approximate to the androgen transdermal therapeutic system. The heating from the temperature modification apparatus raises the temperature of the androgen transdermal therapeutic system and raises the temperature of the patient""s skin to achieve an increased rate of delivery of androgen through the skin. The controlled heat can also be used to adjust dosage rates of the androgen transdermal therapeutic system and to mimic natural circadian patterns. The controlled heating may also be used to improve or regulate the release of androgen from injected/implanted extended/controlled release systems.

1. Field of the Invention
The present invention relates to methods and apparatus for the administration of testosterone and other androgens. More particularly, the present invention relates to using controlled heat to improve administration of testosterone pharmaceuticals.
2. Description of the Prior Art
The dermal administration of pharmaceutically active compounds involves the direct application of pharmaceutically active formulation(s) to the skin, wherein the skin absorbs a portion of the pharmaceutically active compound which is then taken up by the blood stream. Such administration has long been known in the practice of medicine and continues to be an important technique in the delivery of pharmaceutically active compounds. For example, U.S. Pat. No. 4,286,592, issued Sep. 1, 1981, to Chandrasekaran shows a bandage for administering drugs to a user""s skin consisting of an impermeable backing layer, a drug reservoir layer composed of a drug and a carrier, and a contact adhesive layer by which the bandage is affixed to the skin.
For some drugs, such dermal administration offers many important advantages over other delivery techniques, such as injection, oral tablets, and capsules. These advantages include being noninvasive (thus, less risk of infection), avoiding first pass metabolism of the drug in the liver when the drug is taken orally and absorbed through the gastrointestinal tract, and improved control of the concentration of pharmaceutically active compounds in a patient""s bloodstream. In particular, uncontrolled and unwanted variance in concentrations over time are typical in injection and oral administrations and are often associated with undesirable side effects and/or less than satisfactory intended effects.
In recent years there has been an increased interest in noninvasive drug delivery systems such as androgen transdermal therapeutic systems (ATTS). ATTSs offer the advantages of providing controlled release of a drug for a specified period, in contrast to the uncontrolled peaks and troughs produced by oral or parenteral application. Other advantages of these systems include: elimination of gastrointestinal absorption, reduced total dosage, less expensive than intramuscular or intravenous administration where applicable, avoidance of xe2x80x9cfirst passxe2x80x9d inactivation by the liver, use of agents with a narrow therapeutic index, and improved compliance with decreased administration cycle.
The major goals of testosterone replacement therapy are to restore serum testosterone concentrations to within the normal range for healthy men and, if possible, in a way that mimics the normal circadian pattern of endogenous secretion. More specifically it is desirable for the therapy to mimic the natural rise of testosterone level which peaks in the morning followed by gradual decrease, reaching a valley in the evening. Use of a androgen transdermal delivery system to deliver testosterone as disclosed in the present invention in hypogonadal men can achieve this goal. Other therapeutic uses of androgen(s) with the present invention include but are not limited to treatment of hypopituitarism, osteoporosis, menstrual disorders, refractory anemia, promotion of anabolism, and influencing conditions related to puberty.
Male hypogonadism is a disorder whereby testosterone production is reduced below the normal range of 3 to 10 mg/day. Symptoms of this disorder include impairment in:libido, sexual function, energy, mood, as well as regression of secondary sex characteristics and decreases in lean body mass and bone density. Available androgen replacement modalities include intramuscular injection of long-acting testosterone esters and oral administration of alkylated and esterified testosterone. However, neither of these treatments delivers testosterone in a manner which produces plasma levels mimicking normal circadian profiles of the endogenous hormone. Recently several transdermal testosterone systems have been developed. These systems have normalized serum testosterone concentrations over a period of 24 hours and allowed some approximation of the circadian pattern seen in healthy young men. Although these systems have proven useful, they are not without side effects. For example approximately 53 percent of men experience local skin reactions (contact dermatitis) at the application sites after using Androderm(copyright), a testosterone patch, which in some instances necessitates discontinuing use of the patch.
The term xe2x80x9candrogen transdermal therapeutic systemxe2x80x9d or xe2x80x9cATTS,xe2x80x9d as used herein, is defined as an article, apparatus or method for delivery of androgen into the human body via skin permeation. An ATTS is designed for therapeutic and other uses of androgens. The term xe2x80x9cATTSxe2x80x9d in this application, unless otherwise specified, only refers to those systems in which the main driving force for drug permeation is the drug concentration gradient.
The term xe2x80x9candrogen,xe2x80x9d as used herein, is broadly defined to include any pharmaceutically active compound which is capable of regulating masculine secondary sexual characteristics, including but not limited to esters of testosterone such as propionate, phenylacetate, enanthate, cypionate, methyl testosterone, fluoxymesterone, methandrostenolone, 17 alpha-methylnortestosterone, norethandrolone, stanolone, oxymetholone, stanozolol, ethylestrenol.
Additionally, androgens include pharmaceutically active agents which promote growth, such as an increase in height and development of skeletal musculature, thickening of the skin, proliferation of sebaceous glands, as well as loss of subcutaneous fat, growth of axillary and body hair, growth of the larynx, growth of beard and initiating the onset of male pattern baldness. Androgens may also be generally described as pharmaceutical agents acting on the pituitary, testes and sebaceous glands or an agent which has nitrogen retaining anabolic effects.
The term xe2x80x9cskin,xe2x80x9d as used herein, is defined to include stratum corneum covered skin and mucosal membranes.
In an ATTS, an androgen is usually contained in a formulation, such as a hydro-alcohol gel, and may include a rate limiting membrane between the formulation and skin for minimizing the variation in the permeation of the androgen. When an ATTS is applied to skin, the androgen begins to transport out of the formulation, and transport across the rate limiting membrane (if present). The androgen then enters the skin, enters the blood vessels and tissues under the skin, and is taken into the systemic circulation of the body by the blood. An ATTS may have certain amounts of androgen in or on the skin side (the bottom side) of the rate limiting membrane (if present) prior to use. For example, some of the drug may be present in an adhesive on the bottom side of the rate limiting membrane. In those ATTS""s, that portion of the androgen on the skin side of the rate limiting membrane will enter the skin without passing through the rate limiting membrane.
After placing an ATTS on the skin, the androgen concentration in the blood typically remains unchanged from the natural levels for a period of time, before starting to gradually increase and reach a concentration deemed to be medicinally significantly beneficial, called the xe2x80x9ctherapeutic levelxe2x80x9d (the time it takes to reach the therapeutic level is referred to hereinafter as the xe2x80x9conset time.xe2x80x9d). The onset time and the delivery rate of the androgen into the targeted area(s) of the body for a typical ATTS are usually determined by several factors, including: the rate of release of the androgen from the formulation, the permeability of the androgen across the rate limiting membrane (if a rate limiting membrane is utilized), the permeability of the androgen across the skin (especially the stratum corneum layer), androgen storage in and release from the depot sites, the permeability of the walls of the blood vessels, and the circulation of blood and other body fluid in the tissues (including the skin) under and around the ATTS.
While an ATTS works well in many aspects, current dermal androgen delivery technology has some serious limitations, including: 1) the long onset time; 2) the skin permeability being so low so that a strong permeation enhancing agent has to be used to increase skin permeability, which tends to cause serious skin irritation.
It is known that elevated temperature can increase the absorption of drugs through the skin. U.S. Pat. No. 4,898,592, issued Feb. 6, 1990, to Latzke et al., relates to a device for the application of heated transdermally absorbable active substances which include a carrier impregnated with transdermally absorbable active substance and a support. The support is a laminate made up of one or more polymeric layers and optionally includes a heat conductive element which is used for distribution of the patient""s body heat such that absorption of the active substance is enhanced. U.S. Pat. No. 4,230,105, issued Oct. 28, 1980, to Harwood, discloses a bandage with a drug and a heat-generating substance, preferably intermixed, to enhance the rate of absorption of the drug by a user""s skin. Separate drug and heat-generating substance layers are also disclosed. U.S. Pat. No. 4,685,911, issued Aug. 11, 1987, to Konno et al., discloses a skin patch including a drug component, and an optional heating element for melting the containing formulation if body temperature is inadequate to do so.
However, it would be advantageous to develop methods and apparatus to improve the androgen administration of ATTSs, to better accommodate various clinical needs, and to minimize side effects. For example it would be advantageous to develop a drug delivery system that can elevate skin temperature to a desired temperature range. The desired temperature range should be a range which improves the administration of the androgen, but does not significantly increase the chances of trauma to the skin due to overheating. Similarly it would be advantageous to provide elevated temperatures within a prescribed range which can be altered or adjusted within the range as needed. Having an adjustable temperature would allow a patient or caregiver greater control over the absorption rate. Furthermore it would also be advantageous to provide an elevated temperature for a controlled period of time or a desired duration. It would also be advantageous to develop a method and apparatus to allow the patient or caregiver to freely select the site on the skin where temperature is to be elevated.
The present invention relates to the methods and apparatus for improving transdermal administration of testosterone pharmaceuticals through the use of controlled heat.
In the application of an androgen transdermal therapeutic system, such as the Androderm(copyright) (testosterone transdermal system manufactured by TheraTech, Inc., the absorption of the androgen is usually determined by a number of factors including: the diffusion coefficient of androgen molecules in the drug formulation, the concentration of dissolved androgen in the formulation, the skin permeability to the androgen, androgen storage in and release from the depot sites (sites in the skin and/or sub-skin tissues in which dermally-absorbed androgen molecules are stored before being gradually released into other parts of the body), the body fluid (including blood) circulation in the skin and/or other tissue under the skin, and permeability of the walls of capillary blood vessels in the sub-skin tissues. Thus, in order to address the limitations of the current dermal androgen delivery technologies, it is desirable to have control over and have the capability to favorably influence these factors. It is believed that controlled heating can potentially favorably affect each one of the above factors for more efficient delivery of androgen.
Specifically, increased temperature generally can increase diffusion coefficients of the androgens in the formulations and their permeability across the skin. Increased heat also increases the blood and/or other body fluid flow in the tissues under the ATTS, which should carry the drug molecules into the systemic circulation at faster rates. Additionally, increased temperature also increases the permeability of the walls of the capillary blood vessels in the sub-skin tissues. Thus, the present invention uses controlled heating to affect each of the above factors for obtaining controllable dermal absorption of androgens.
Skin irritation is a major problem with ATTSs currently on the market. The skin irritation is believed to be mainly caused by a permeation enhancer in the formulation. (In the case of Androderm(copyright), the permeation enhancer is monoglyceral oleate). The permeation enhancer is needed to increase skin permeability so that sufficient testosterone can permeate across the skin. The degree of skin irritation is usually positively correlated with the permeation enhancer concentration in the formulation and contact time with the skin. Since controlled heat can significantly increase dermal skin absorption, it is conceivable that, with controlled heat, one may be able to reduce the concentration of the enhancer in the formulation, reduce the contact time between the formulation and the skin, and/or use a milder permeation enhancer. Properly doing so should reduce skin irritation while still delivering sufficient testosterone. In other words, using controlled heat can shift at least some burden to enhance skin permeability from permeation enhancer to heat, which is a much safer way to enhance skin permeability.
This invention provides novel methods and apparatus for controlled heating (hereinafter xe2x80x9ctemperature control apparatusxe2x80x9d) during the application of the ATTS, such that heating can be initiated, maintained and terminated to accommodate the patient""s needs. Through the proper selection of the moment(s) to initiate controlled heating, the heating temperature, the moment(s) to increase or decrease the temperature, and moment(s) to stop the controlled heating, the following control/manipulation of the absorption rates can be achieved: 1) the onset time of the androgen in the ATTS can be shortened; and 2) the androgen absorption rate throughout a selected period of duration or throughout the entire duration of the ATTS application can be increased.
The present invention also relates to methods and apparatus for using an insulating device, such as a cover made of insulating material (i.e. closed-cell foam tape) with adhesive edges, and a size slightly larger than the ATTS to cover the ATTS when the ATTS and the skin of the user is exposed to extreme temperature (i.e. hot shower or hot tub bath; direct sunshine).
One of the more important aspects of the present invention is the apparatus for generating and providing controlled heating. The controlled heat generating apparatus generally comprises temperature regulating mechanism such as a heat generating medium and means to pass the heat generated by the heat generating medium to the ATTS, the skin, and/or the sub-skin depot and storage sites. A controlled heat generating apparatus generally further includes a mechanism (such as tape, adhesive, and the like) for affixing the apparatus onto the ATTS and/or the skin. Preferably, the affixation mechanism securely holds the controlled heat generating apparatus in place while in use, but also allows relatively easy removal after use. Additionally, the controlled heat generating apparatus may further include a mechanism for reducing and/or terminating the generation of heat. When the heat generating apparatus is used in conjunction with an ATTS, the shape and size of the controlled heat generating apparatus may be specially made to accommodate the ATTS with which they are to be employed.
Controlled elevation of skin temperature provides specific advantages over the prior art. For example, the present invention provides elevation of skin temperature within a predetermined temperature range. In one embodiment, this predetermined temperature range is made possible by providing an oxidation reaction within a compartment having a controlled permeability to oxygen. By varying the compartment""s permeability to oxygen, the temperature elevation caused by the oxidation reaction can be controlled or more precisely regulated within the predetermined narrow range. The duration of the elevated temperature can be controlled by removing the device entirely from the skin, by preventing oxygen from entering the compartment containing the oxidation reactants, or by providing a predetermined amount of oxidation reactants which will generate heat for a given amount of time when exposed to oxygen. Furthermore the heating site may be freely selected where the heating apparatus is not incorporated with the ATTS. Thus, the present invention provides controlled heating.
One embodiment of a temperature control apparatus is a shallow chamber including air impermeable side wall(s), a bottom wall, and an air impermeable top wall which has area(s) with limited and desired air permeability (e.g., holes covered with a microporous membrane or a membrane with a specific rate of permeability to oxygen). A heat generating medium is disposed within the shallow chamber. The heat generating medium preferably comprises a mixture of iron powder, activated carbon, salt, water, and, optionally, sawdust. The controlled heat generating apparatus is preferably stored in an airtight container from which it is removed prior to use. After removal from the airtight container, oxygen in the atmosphere (xe2x80x9cambient oxygenxe2x80x9d) flows into the heat generating medium through the areas on the air impermeable top with desired air-permeability to initiate a heat generating oxidation reaction (i.e., an exothermic reaction). The desired heating temperature and duration can be obtained by controlling the flow air through the top (e.g., selecting the right size and number of holes on the cover and/or selecting the microporous membrane covering the holes for a specific air permeability), and/or by selecting the right quantities and/or ratios of components of the heat generating medium. Air flow through the sides of the chamber may be additionally or alternatively controlled in like manner.
This embodiment of the controlled heat generating apparatus preferably includes a mechanism for affixing the controlled heat generating apparatus onto the skin or an ATTS that is applied to the skin. For applications where the removal or termination of the heating might be necessary, the heat generating apparatus may also have a mechanism for allowing easy removal from the ATTS and/or the skin or for termination of the heating. One mechanism for allowing easy removal of the heat generating apparatus from an ATTS without removing the ATTS from the skin comprises a layer of adhesive on the side walls of the heat generating apparatus with an nonadhesive area or less adhesive area (less adhesive than the adhesive affixing the ATTS to the skin) at the bottom of the shallow chamber. The non- or less adhesive area may have a shape similar to that of the ATTS. When such a heat generating apparatus is applied onto the ATTS which is on the skin, the adhesive at the bottom of the side walls of the heat generating apparatus adheres to the skin, and non- or less adhesive part is on top of, but not adhered or not strongly adhered to the ATTS. This allows for removal of the heat generating apparatus without disturbing the ATTS.
In the present invention, means for preventing heat loss is also provided. Means for preventing heat loss includes insulating materials used in the drug delivery and temperature control components. Other means for preventing heat loss include using adhesives and other means for securing and sealing the heat generating apparatus patch to the skin of the user and the ATTS so that heat does not escape through unsecured edges or corners of the drug delivery system, as well as customized shaping or molding of the heat generating apparatus patch to more appropriately fit an ATTS or a specific part of the user""s body. For example, a heat generating apparatus patch may have a substantially oval shape. The oval shape facilitates the prevention of heat loss through unsecured corners by eliminating corners which may be difficult to secure and result in heat loss.
Another embodiment of the present invention provides a foam cover for the heat generating apparatus patch. The foam tape cover has insulative properties which help to prevent heat loss through the cover and which help to prevent varying ambient temperatures from adversely affecting the heat generated by the heat generating apparatus patch. Moreover, an insulative cover capable of insulating the exposed surfaces of the heat generating apparatus patch and ATTS is also contemplated.
Although one application of such a heat generating apparatus is to be used in connection with an ATTS, it is understood that the heat generating apparatus can also be applied directly to the skin to increase the release of drugs from depot sites or sites of injection or implantation of controlled released drugs (storage sites), or to accelerate the absorption of subcutaneously or intramuscularly injected androgens.
The heat generating mechanism of the present invention for the controlled heat generating apparatus is not limited to the preferred exothermic reaction mixture of iron powder, activated carbon, salt, water, and, optionally, sawdust, but may include a heating unit whose heat is generated by other exothermic chemical reactions.
Similarly, an electric heating unit may be used. The electric heating unit, preferably, includes a two dimensional surface to pass the heat to the ATTS and/or the skin. The electric heating unit may also include a temperature feedback system and temperature sensor that can be placed on the ATTS or the skin. The temperature sensor monitors the temperature at the ATTS or skin and transmits an electric signal based on the sensed temperature to a controller which regulates the electric heating unit to keep the temperature at the ATTS or skin at desired levels. Preferably, a double sided adhesive tape can be used to affix the electric heating unit onto the skin.
The heat generating mechanism may also comprise an infrared generating unit and mechanism to direct the infrared radiation onto the ATTS or the skin. It may also have a temperature feedback system and temperature sensor that can by placed on an ATTS or the skin to control the intensity of the infrared emission in order to maintain the temperature at the ATTS or skin at desired levels.
The heat generating mechanism may further comprise a microwave generation unit and a mechanism to direct the microwave radiation onto the ATTS or the skin. Again, the heat generating mechanism may have a temperature feedback system and a temperature sensor to regulate the intensity of the microwave emission to maintain the temperature at the ATTS or skin at desired levels.
It is an object of some embodiments of the present invention to provide an apparatus for increasing the diffusion coefficient of androgen molecules in drug formulations used in a transdermal drug delivery system.
It is an additional object of some embodiments of the present invention to provide a method and apparatus for increasing the skin permeability to the androgen of a transdermal drug delivery system.
It is yet another object of some embodiments of the present invention to provide a method and apparatus for manipulating the storage and release of the androgen from depot sites with controlled heat.
It is yet a further object of one embodiment of the invention to provide a method and apparatus for increasing body fluid circulation near a drug delivery site thereby increasing entrance of a drug formulation into systemic circulation with controlled heat.
It is yet an additional object of some embodiments of the present invention to provide a method and apparatus for increasing the permeability of the walls of capillary blood vessels in subskin tissues for facilitating uptake of dermally absorbed androgen into the systemic circulation.
It is still another object of some embodiments of the present invention to reduce the concentration of a permeation enhancer used in a transdermal drug delivery system and reduce contact time between the skin of a patient and the drug formulation used in a transdermal drug delivery system, particularly a system having a permeation enhancer, while still delivering a sufficient amount of androgen via skin permeation.
It is still further an object of some embodiments of the present invention to provide a method and apparatus for using a mild permeation enhancer in a transdermal drug delivery system while still delivering sufficient androgen.
It is still an additional object of one embodiment of present invention to provide a method and apparatus for shifting the burden to enhance permeability and improve performance of a transdermal drug androgen system from the permeation enhancer to heat.
It is another object of some embodiments of the present invention to provide a method and apparatus which can more closely mimic circadian patterns as they relate to androgen concentration within the blood stream.

Methods and apparatus for improved administration of testosterone pharmaceuticals


A high-concentration sewage treatment system for self-sufficiency of energy is provided. The system includes a hydrolysis acidification device, an anaerobic reactor, a sludge treatment device, a desulfurization tower, and a biogas power generation device. The hydrolysis acidification device includes a hydrolysis acidification tank, a first sedimentation tank, a first overflow water tank and an overflow pipe. The sludge treatment device includes a second sedimentation tank, a second overflow water tank, an inlet pipe and a dissolved oxygen meter. The second overflow water tank communicates with the hydrolysis acidification tank through a return pipe. The inlet pipe defines a jet hole. A regulating valve is connected to the inlet pipe. The regulating valve controls a speed and a height of mixed liquid in the jet hole. A high-concentration sewage treatment method for self-sufficiency of energy is also provided.

The conventional anaerobic sludge reactor has UASB, EGSB, IC, etc. A principle of wastewater treatment is basically that sewage to be treated is introduced into the reactor as uniformly as possible. The sewage in the reactor and granular or flocculent sludge react and produce biogas (mainly methane and carbon dioxide) to adhere to sludge. As the biogas moves upwards, it hits the three-phase separator to achieve three-phase separation of solid, liquid and gas. Anaerobic sludge reactors are also widely used in wastewater treatment in different fields due to their different specificity.
However, above anaerobic sludge reactor has two disadvantages. On the one hand, the sewage needs to be subjected to hydrolysis acidification treatment before entering the anaerobic sludge reactor, and the hydrolysis acidification treatment tends to cause the sewage to have higher acidity, thereby inhibiting the anaerobic sludge reactor, which is not conducive to improve the treatment efficiency of sewage in the anaerobic sludge reactor and thus leads to a decrease in the overall treatment efficiency. Although the acidity can be reduced by pH adjustment during the hydrolysis acidification process, it is easy to increase cost. On the other hand, the anaerobic sludge reactor sewage treatment energy consumption is large, which is not conducive to save energy.

High-concentration sewage treatment system and method for self-sufficiency of energy

Wuhan Huizhong Dachuan Automatic Control Equip. Co


An optical module with a plurality of optical waveguide substrates having element mounting openings and end surfaces which are adhered to each other with an optical adhesive; and a plurality of light deflecting element arrays mounted to the respective element mounting openings of the plurality of optical waveguide substrates, the plurality of light deflecting element arrays including a plurality of light deflecting elements.

In recent years, an optical switch module, using a light deflecting element having an electro-optical effect, has been proposed (for example, refer to the U.S. Pat. No. 6,504,966).
Such an optical switch module has the following structure. As shown in, for example, FIGS. 1A and 1B, in the optical switch module, light deflecting elements 101 and 102, formed of electro-optical materials (for example, electro-optical crystals, such as PZT or PLZT), are mounted onto a slab optical waveguide substrate unit 100.
That is, as shown in, for example, FIGS. 1A and 1B, the slab optical waveguide substrate unit 100 has integrally formed, input channel optical waveguides (input channel optical waveguide array) 103 to which a light signal is input, collimator lenses (input-side lens array) 104 that convert the input light signal into parallel light (collimated light), a slab optical waveguide 105 that allows the light signal converted into the parallel light to propagate therethrough, light-converging lenses (output-side lens array) 106 that converge the light signal (propagating parallel light), and output channel optical waveguides (output channel optical waveguide array) 107 to which the light signal is output. A first light-deflecting element mounting opening 112, to which the light deflecting elements 101 are mounted, and a second light-deflecting element mounting opening 113, to which the light deflecting elements 102 are mounted, are formed in the slab optical waveguide array substrate unit 100. In FIG. 1B, reference numeral 111 denotes a core layer, reference numeral 114 denotes a lower clad layer, and reference numeral 115 denotes an upper clad layer.
The input-side light deflecting elements (first light-deflecting element array) 101 and the output-side light deflecting elements (second light-deflecting element array) 102 are formed by forming thin-film slab optical waveguides 109, formed of electro-optical materials (for example, electro-optical crystals, such as PZT or PLZT), onto respective conductive substrate units 108; by forming prism electrodes 110 on a surface of each slab optical waveguide 109; and by polishing end surfaces.
In the optical switch module, the input-side light deflecting elements 101 are mounted to the first light-deflecting element mounting opening 112 disposed between the collimator lenses 104 and the slab optical waveguide 105 at the slab optical waveguide substrate unit 100. The output-side light deflecting elements 102 are mounted to the second light-deflecting element mounting opening 113 disposed between the slab optical waveguide 105 and the light-converging lenses 106.
In the optical switch module having such a structure, application of a predetermined voltage to the prism electrodes 110 (formed at the input-side light deflecting elements 101 and the output-side light deflecting elements 102) results in the following. For example, as shown in FIG. 1A, light signals, input from the input channel optical waveguides 103 and converted into parallel lights by the collimator lenses 104, are deflected by the input-side light deflecting elements 101, propagate through the slab optical waveguide 105, are deflected again by the output-side light deflecting elements 102, are converged by the light-converging lenses 106, and are focused at the predetermined output channel optical waveguides 107. This causes a path of the light signal that is input from the input channel optical waveguide 103 to be switched, so that the light signal is output from the predetermined output channel optical waveguide 107.
An example of a method of manufacturing the optical switch module having the above-described structure is given below. First, as shown in, for example, FIG. 2A, a slab optical waveguide substrate unit 100 is formed so that input channel optical waveguides 103, an input-side lens array 104, a first light-deflecting element mounting opening 112, a slab optical waveguide 105, a second light-deflecting element mounting opening 113, an output-side lens array 106, and an output channel optical waveguide 107 are integrally formed. Next, as shown in, for example, FIGS. 2B and 2C, a first light-deflecting element array 101 and a second light-deflecting element array 102 are mounted to the light-deflecting element mounting opening 112 and to the light-deflecting element mounting opening 113 in a slab optical waveguide substrate unit 100, respectively. (For example, refer to the U.S. Pat. No. 6,504,966).
In this manufacturing method, since the number of joints that are joined with an adhesive is small, it is possible to restrict the influence resulting from positional displacement with time at the joints. For mounting the light deflecting element arrays 101 and 102 onto the slab optical waveguide substrate unit 100, active alignment is performed while monitoring the intensity of output light. During the active alignment, when light (monitor light, propagating light) that propagates through the slab optical waveguide is displaced from a predetermined traveling angle, the propagating light does not combine at the output channel optical waveguides 107, and positional adjustment of the output-side lens array (light-converging lens array) 106 cannot be carried out either. Therefore, it is difficult to perform the alignment (active alignment) of the first light-deflecting element array 101 and the second light-deflecting element array 102.
The causes of the angular displacement of the propagating light are, for example, polishing precision of the light deflecting elements and crystal characteristics (ununiformity in film thicknesses and refractive indices) of the light deflecting elements.
Another example of manufacturing the optical switch module is given below. For example, as shown in FIGS. 3A to 3D, each component making up the optical switch module is individually formed. The components are located where an input channel optical waveguide array 103 and an input-side lens array 104 are formed, the component where a first light-deflecting element array 101 is mounted, the component where a slab optical waveguide 105 is formed, the component where a second light-deflecting element array 102 is mounted, and the component where an output-side lens array 106 and an output channel optical waveguide array 107 are formed. These components are joined to each other with a butt-joint, so that the optical switch module is manufactured. (For example, refer to the U.S. Pat. No. 6,504,966).
In this manufacturing method, it is possible to join each component as a result of active alignment while monitoring the intensity of output light. However, the characteristics of the optical switch module may become deteriorated due to positional displacement with time at each joint. In particular, if the number of such joints is large, the characteristics of the optical switch module tend to be deteriorated due to positional displacement with time at each joint.
Accordingly, the related art has the problem that alignment by active alignment cannot be reliably performed due to an angular displacement of propagating light.

Optical module and method of manufacturing the same


The present invention relates to a liquid gas level measuring system for use in a liquid gas tank and designed to cooperate with a float level gauge head mounted on the gas tank and made of magnetically inert material. The system comprises a dial module 1 attachable to the float level gauge head and a sensor module 2 releasably connected to the dial module 1. The dial module 1 is provided with at least one directing dial magnet 103 magnetically coupled with a drive magnet of the float level gauge. The sensor module includes a Hall effect sensor, a battery 204 and a radio module with an antenna 205, allowing wireless measurement data transmission to a remote location.

LPG is used both in various types of industrial installations and in households. From the viewpoint of a gas supplier acquiring new clients and keeping the old ones requires continuous monitoring the actual gas consumption as well as gas level in tanks. These measurements are carried out either periodically in predetermined cycles or on demand, while the measurement results are either determined by visual inspection of rotatable indicator dials provided in measurement heads mounted on the tanks or are transmitted telemetrically.
In mechanical float level gauges commonly used nowadays an element floating on surface of a liquid gas (or other liquid medium) is arranged on a rotating arm provided with a gear transforming the arm rotation in a horizontal axis to a corresponding rotation of a vertically arranged element around a vertical axis. At the uppermost point of the rotating vertical element, in a possibly small distance from the float level gauge head made of magnetically inert material and tightly closing the tank opening, a magnet is arranged, so that magnetic field changes direction corresponding to rotation of the vertical element. A magnetic dial a scale defining the tank filling degree in form of a magnetic dial is mounted on the float level gauge head. A rotary element such as dial disc or a gauge pointer is changing its position according to the changes of the magnetic field direction, and thus showing the floating element position corresponding to the liquid medium present in the tank. Such float level gauges are considered reliable due to relatively simple mechanical construction, but they require direct visual inspection of the dial to retrieve the actual gas level status.
US 2004/0079152 A1 discloses an electrical system for measuring liquid gas amount in a tank, the system comprising a set of magnetic sensors, a temperature measurement module provided with a microprocessor with a radio module, wherein magneto-resistive transducers of magnetic field are used, having sensitivity higher than Hall effect sensors (can determine smaller fields), but being capable of measuring only small field ranges. Radio module allows to send measurement results to a remote location. However, even use of a few magnetic sensors arranged in various distance from the magnet does not guarantee a reliable operation in case of various types of level indicators.
US 2006/243345 A1 discloses a wireless tank level monitoring system utilizing a Hall effect sensor and having a base station with a battery status control connected to a radio module.
Further, in US 2004/0129075 A1 a remote fluid level detection system is disclosed, wherein a microcontroller-based electronic circuit comprising a magnetic field sensor (such as GMR AA002-02 available from NVE Corporation) detects orientation of the magnetic field generated by a single permanent magnet inside the existing gauge mechanism. The system includes a tank module comprising a housing, a battery cover, battery units, a microcontroller, a circuit board, an RF transmitter, a magnetic sensor, an attachment band, electrical connection wires, a momentary switch, an electric inclinometer, a liquid crystal display, a clock oscillator, and a voltage regulator. The tank module housing is dimensioned to fit over the pre-existing tank gauge and is secured to the gauge by means of the attachment band. The gauge is mounted on the top of the tank by mounting bolts, connecting the gauge housing to the tank, and the gauge face comprises a simple compass tracking the magnet position.
Yet further, US 2009/0243863 A1 discloses a cellular tank level monitor for liquefied gas and cryogenic liquids, the monitor being configured to be magnetically attached to the fuel tank and operatively connected to a Hall effect module.
US 2009/0160674 A1 discloses a wireless telemetry system consisting of a sensor (such as a customary Hall effect sensor) generating an electrical signal indicative of the level and/or usage, a wireless transmitter transforming this signal into an signal compatible with Wi-Fi (802.11a/b/g/n) transmission protocol, and a Wi-Fi wireless router receiving this WiFi signal and storing it on a host computer for subsequent transmission to a server computer located at a distant location over the public internet.
Moreover, in U.S. Pat. No. 6,679,116 B2 a liquid level gauge, assembly including a dial assembly having a shaped magnet and a removable magnetic detector with a Hall effect sensor. In this assembly the Hall effect sensor is connected to a dial with a cable. Further, a measurement of magnetic field is based on detection of rotation of a shaped magnet being magnetically coupled to a tank (gauge) magnet rotating in response to movements of the float arm.
U.S. Pat. No. 8,294,457 B2 discloses a rotary magnetic encoder assembly comprising a magnetic field sensor arrangement, a rotatable magnet disposed adjacent the magnetic field sensor arrangement and having a magnetic field that is sensible by the magnetic field sensor arrangement, and a rotary encoder shaft that effects rotation of the rotatable magnet without contacting the rotatable magnet.
In U.S. Pat. No. 6,564,632 B2 a liquid level gauge assembly is disclosed including a dial assembly having a shaped magnet and a removable magnetic detector with a magnetic sensor, preferably a Hall sensor. The dial assembly is capable of providing both visual and electrical output signal related to the liquid level measured by the gauge assembly. The shaped magnet has a variable thickness which, in cooperation with the Hall sensor, provides a linear output signal from the detector over more than 270 degrees. The dial assembly cover is provided with a cover having a channel-like socket adapted for receiving a Hall sensor-containing detector connected by an electric cable to external devices.
Despite numerous systems for measuring liquid gas level using magnetic field sensors and wirelessly transmitting the measurement results to a remote location there is a constant need for further improvements. The areas of improvements involves optimizing the balance between sensitivity and measurement range of a magnetic field sensor, eliminating the elements prone to damage (such as cables connecting component modules of the measurement system), increasing safety of utilizing the liquid gas level measuring systems and also reducing costs of manufacturing of and installing such smart metering devices.
The above-mentioned safety-related issues include the following problem. Several prior art liquid gas level smart metering devices are formed so as to be mounted on a float level gauge head in place of a simple mechanical dial gauge, which require visual inspection. As a rule such installation is made by means of two cross screws going through two corresponding lugs provided in the lower part of the device housing and engaging the respective threaded holes in the level gauge head. Many end users tend to replace the analogue dial indicators with such devices on their own, using inappropriate tools (such as multi-purpose tools instead of dedicated screwdrivers) or even erroneously manipulating other screws (such as hex(interior) screws commonly used to fix the level gauge head to a tank). This involves increased risk of damaging the devices, unsealing the tanks, dismantling the gauge and releasing the gas, which eventually may result in an explosion. Thus, a need has been observed and identified by the present inventors to provide a system that would allow the end users to change the sensor devices easily (for example in order to replace batteries or damaged electronic modules), while eliminating the need for detaching/attaching modules directly connected to a pressurized gas tank.