Disclosed are substantially purified Plasmodium sporozoites and preparations of Plasmodium sporozoites substantially separated from attendant non-sporozoite material, where the preparations of Plasmodium sporozoites have increasing levels of purity. Vaccines and pharmaceutical compositions comprising purified Plasmodium sporozoites are likewise provided. Methods of purifying preparations of Plasmodium sporozoites are also provided.

1. Field of the Invention
This application relates to purification of eukaryotic pathogens and parasites, particularly, Plasmodium sporozoite-stage parasites. More particularly it relates to substantially pure parasites and methods of preparing and using them. The application also relates to vaccine and pharmaceutical compositions of purified sporozoite stage Plasmodium parasites, both attenuated and non-attenuated, and methods of using the compositions in vaccines and other preparations to prevent malaria and other diseases, treat diseases, and as a means to infect volunteers in the testing of malaria vaccines and drugs.
2. Background Art
Malaria is a disease that is estimated to affect 300-500 million people and kills 1-3 million individuals annually. It also has an enormous economic impact on people in the developing world, especially those in sub-Saharan Africa. Plasmodium falciparum accounts for the majority of deaths from malaria in the world. The World Tourist Organization reported that of the nearly 700 million international tourist arrivals recorded worldwide in 2000, approximately 9 million were to West, Central or East Africa, 37 million were to South-East Asia, 6 million to South Asia and 10 million to Oceania. It is estimated that more than 30,000 travelers from North America, Europe, and Japan contract malaria per year. For more than 100 years during every military campaign conducted where malaria was transmitted, U.S. forces have had more casualties from malaria than from hostile fire. An estimated 12,000,000 person days were lost during World War II and 1.2 million during the Vietnam conflict due to malaria.
Transmission of the Plasmodium parasite occurs through the bite and feeding of infected female Anopheles mosquitoes which are active from dusk to dawn. Plasmodium, at the sporozoite stage of development, migrate from the bite site to the liver, primarily via the blood stream, where they multiply within hepatocytes, producing, in the case of P. falciparum, about 10,000-40,000 progeny per infected cell. These liver stage parasites express some proteins which are not expressed at the sporozoite stage. At this stage, parasites re-enter the blood stream as merozoites, expressing some proteins which are different from those expressed during the sporozoite and early hepatic stages, and invade erythrocytes, where additional multiplication increases parasite numbers by approximately 10 to 20 fold every 48 hours. Unlike the five to ten day development in the liver, which does not induce any symptoms or signs of malaria, untreated blood stage infection causes hemolysis, shaking chills, high fevers, and prostration. In the case of P. falciparum, the most dangerous of the four major species of Plasmodium that cause human disease (P. vivax, P. malariae, and P. ovale [P. knowlesi can also cause human disease]), the disease is complicated by disruption of microcirculatory blood flow and metabolic changes in vital organs such as the brain, kidneys and lungs, frequently leading to death if not urgently treated.
An effective vaccine against P. falciparum malaria remains one of the great challenges of medicine. Despite over one hundred years of effort, hundreds of millions of dollars in research, lifelong sacrifice from dedicated physicians and scientists, and many promising experimental vaccines, there is no marketed vaccine to alleviate one of the great infectious scourges of humanity.
A generation ago, public health initiatives employing chloroquine, DDT and vector control programs seemed poised to consign falciparum malaria to insignificance as a worldwide menace. The lack of an effective vaccine complicated these efforts, but sustainable control seemed imminent.
The promise of impending success was short-lived and the reasons for failure were multi-factorial. The parasites grew increasingly resistant to highly effective and affordable anti-malarial medications, vector control measures lapsed, and trans-migration, war and economic disruption became increasingly more common in endemic areas of the developing world. As a result, P. falciparum malaria resurged, annually placing at least 2.5 billion humans at risk, causing 300-900 million infections, and killing 1-3 million people. Of the many social, economic, environmental and political problems that afflict the developing world, P. falciparum malaria is increasingly seen as both a root cause and cruel result of these inequities, and is a singular impediment to solving these complex problems. Controlling P. falciparum malaria in the developing world may not be possible without an effective vaccine. In practice, given social, political and economic realities, we believe that a vaccine may be an essential component of a sustainable control program, and will be required for a global eradication campaign.
During the last 25 years most research effort has been spent on identifying the antigenic subunits of the parasite which confer immunity—unfortunately, with less than satisfying results. This effort and the attendant difficulties in developing a suitable vaccine have been described (Nussenzweig V., F. and R. S. Nussenzweig, Adv. Immunol., (1989) 45: 283-334; Hoffman S. L. et al. In: Hoffman S. L., ed. Malaria Vaccine Development: A Multi-Immune Response Approach (1996) Washington, D.C.: ASM Press, pp. 35-75; Hoffman S. L. and L. H. Miller, In: Hoffman S. L., ed. Malaria Vaccine Development: a Multi-Immune Response Approach (1996) Washington, D.C.: ASM Press, pp. 1-13; Epstein, J. E. et al, Curr. Opin. Mol. Ther. (2007) 9:12-24; Richie, T. L. & A. Saul, Nature, (2002) 415:694-701).
There are continuing efforts to produce subunit malaria vaccines. Typical of such attempts, Paoletti et al. (U.S. Pat. No. 5,766,597, issued Jun. 16, 1998) disclose a recombinant poxvirus containing DNA from Plasmodium coding for one or more circumsporozoite proteins, including an embodiment termed NYVAC-Pf7, possibly useful as a potential malaria vaccine. Subsequent testing of this construct proved to be disappointing (Ockenhouse, C. F. et al. J. Infect. Dis. (1998) 177: 1664-73).
Similarly, another candidate subunit circumsporozoite vaccine was proposed and identified as RTS, S/AS02A (Stoute J. A. et al. J. Infect. Dis. (1998) 178: 1139-44). The results of the first Phase 2b field trial of this vaccine in one-four year old children in Mozambique was reported (Alonso, P. L. et al. Lancet (2004) 364:1411-1420; Alonso, P. L. et al. Lancet (2005) 366:2012-2018; Epstein, J. E. et al, Supra; Richie, T. L., F. & A. Saul, Supra), as were the results of other Phase 2b field trials in infants (Aponte, J. J. et al. (2007) The Lancet 370:1543-1551; Bejon, P. et al (2008) NEJM 359:2521-32; Abdullah, S et al (2008) NEJM 359:2533-44. The vaccine has demonstrated modest protective efficacy.
On the other hand, the demonstration of the effectiveness of whole parasite, radiation attenuated sporozoites (delivered to human hosts by mosquito exposure and to animal hosts by intravenous (i.v.) inoculation) in conferring high levels of protective immunity when recipients are subsequently challenged with pathogenic parasites (most importantly attenuated Plasmodium falciparum to human hosts) was an early milestone in the quest for a suitable vaccine (Hoffman S. L. et al., J. Infect. Dis. (2002) 185: 1155-64). Eventually, this led to efforts to explore the technical hurdles which present themselves in transforming these earlier observations into a practical vaccine approach comprising aseptic attenuated sporozoites (Luke, T. C. & S. L. Hoffman, J. ExP. Biol., (2003) 206:3803-3808; Hoffman, S. L., and T. C. Luke U.S. Pat. No. 7,229,627 and U.S. Publication 2005/0208078). It has also led to increased interest generally in the utility of vaccines utilizing attenuated sporozoites (Menard, R., Nature 2005) 433:113-114; Waters, A. P. et al. Science. (2005) 307:528-530; Wykes, M. F. & M. F. Good, Int. J. Parasitol. (2007) 37:705-712; Renia, L. et al, Expert Rev. Vaccines, (2006) 5:473-481; Epstein, J. E. et al, Supra).
Other modes of attenuation have also been demonstrated. For example, It was shown that attenuated sporozoites resulting from gene alteration of Plasmodium berghei protects mice against P. berghei malaria (Kappe et al. U.S. Pat. No. 7,122,179; Mueller et al. Nature (2005); Mueller, et al. PNAS (2005); van Dijk et al. PNAS (2005) 102:12194-12199); Waters, U.S. Pat. No. 7,550,138; Labeled et al. Infect. And Immun. (2007). Recently genetic attenuation of the sporozoites of P. falciparum has be disclosed (van Schaijk et al. PLoS ONE (2008) 3:e3549); VanBuskirk et al. PNAS.
Similarly, chemical attenuation of Plasmodium has be described (Purcell et al. Infect. Immun. (2008)76:1193-99; Purcell et al Vaccine (2008) 26:4880-84).
Others have also described methods of culturing unpurified preparations of sporozoites and inducing parasite differentiation to axenic liver stages (Kappe et al. US Pub. 2005/0233435).
The studies discussed above set forth certain limitations. For example, while sporozoites delivered to human hosts by the bite of a mosquito generate an effective immune response against malaria, such a method of delivery is clearly not a practical method for vaccinating a population in need of protection against malaria. Additional studies in mice, referred to above, have suggested that the delivery of attenuated sporozoites to mice intravenously are also effective, whereas other means of delivery (e.g., intramuscular) in comparison, are not. An intravenous delivery method, however, is also not practical if a malarial vaccine is to be delivered to numerous individuals (including children and the eldery). Intravenous delivery has increased risks, increased costs, and patients are far less likely to agree to be vaccinated using such a method. Thus, there was a need in the art to provide an effective malarial vaccine that provides protective immunity, where the vaccine can be administered by a variety of methods.
With regard to considerations for human vaccines, the purity of the immunogen and the presence or absence of non-specific, attendant material which may be immunogenic or toxic are further essential issues which have not previously been resolved. Isolated attenuated sporozoite preparations, as used in studies discussed above, contain contaminating and other attendant material. There was a need in the art to develop sporozoite-based vaccines, particularly in humans, that employ aseptically prepared, sterile, purified preparations of sporozoites for use in vaccine compositions. Such aspetically prepared, purified preparations of sporozoites may also be more effective than non-purified preparations when such preparations are administered by non-intravenous delivery methods. (e.g., intramuscular, intraperitoneal, intradermal, epidermal, mucosal, submucosal, cutaneous, or subcutaneous).

Purified plasmodium and vaccine compositions


A cabin is formed as a casing body partitioned and separable from a vehicle body and includes an air purifier for introducing purified air into the casing body to maintain the pressure inside the cabin at a positive level by the air purifier.

A transport apparatus for transporting radiation shielding members and an operator cab structure for this transport apparatus (see, for example, Patent Document 1), and a vehicle (car) with a retrofitted radiation protection device and a vehicle interior structure for this vehicle (see, for example, Patent Document 2) are known as examples of a manned vehicle for special environment use and a cabin structure for this vehicle.
According to FIG. 2 of Patent Document 1, the transport apparatus 5 is configured to run on continuous tracks 8, with an operator cab 9 surrounded by radiation shield plates provided on the continuous tracks 8.
According to FIG. 1 and FIG. 2 of Patent Document 2, the vehicle body 1 has a windshield part 2a covered by a first shielding member 3 and side parts 4 covered by second shielding members 20.    Patent Document 1: Japanese Patent Application Laid-open No. 2001-289990    Patent Document 2: Japanese Patent No. 4268162
Patent Document 1 does not describe in detail the structure of attaching the operator cab 9 on the continuous tracks 8. Substantial alteration may be needed if the shielding capabilities of the operator cab 9 are to be changed in accordance with the level of radiation exposure in the environment, which will increase the cost.
According to Patent Document 2, shielding members are attached to a common vehicle (car), but it would be difficult to cover the entire vehicle completely with shielding members. With no precaution against possible ingress of fine particles of special substances into the vehicle interior, it would also be difficult to provide sufficient countermeasures against special substances.

Manned vehicle and cabin structure thereof


Chlorine is prepared by catalytic oxidation of a hydrogen chloride stream having a content of sulfur in elemental or bonded form of less than 100 ppm, preferably less than 50 ppm, more preferably less than 5 ppm, most preferably less than 1 ppm, based on the weight of the hydrogen chloride stream.

The present invention relates to a process for the preparation of chlorine from a gas mixture containing hydrogen chloride and further secondary components, such as sulfur compounds. The hydrogen chloride employed contains less than 100 ppm, preferably less than 50 ppm, more preferably less than 5 ppm, most preferably less than 1 ppm of sulfur in elemental or bonded form, based on the weight of the gas mixture.
A large number of chemical processes which require chlorine or phosgene as a reactant, such as the preparation of isocyanates or chlorination of aromatics, lead to an unavoidable production of hydrogen chloride. As a rule, this hydrogen chloride is converted back into chlorine by electrolysis (See, e.g., WO 97 24320 A1). Compared with this very energy-intensive method, thermal oxidation of hydrogen chloride with pure oxygen or an oxygen-containing gas over heterogeneous catalysts (the so-called Deacon process) according to4HCl+O22Cl2+2H2Ooffers significant advantages with respect to energy consumption (See, e.g., WO-A-04/0 14 845).
Catalytic oxidation of HCl gas with O2 to give Cl2 and H2O is typically carried out over heterogeneous catalysts. A variety of catalysts, e.g., catalysts based on ruthenium, chromium, copper etc., supported or unsupported may be used. Such catalysts are described, for example, in JP 2001 019405, DE 1 567 788 A1, EP 251 731 A2, EP 936 184 A2, EP 761 593 A1, EP 711 599 A1 and DE 102 50 313 A1. In particular, catalysts based on metallic ruthenium, ruthenium oxide, ruthenium mixed oxide, ruthenium oxychloride and ruthenium chloride, supported or unsupported, can be used. Suitable supports are e.g. tin oxide, aluminum oxide, silicon oxide, aluminum-silicon mixed oxides, zeolites, oxides and mixed oxides (e.g. of titanium, zirconium, vanadium, aluminum, silicon etc.), metal sulfates, alumina. The choice of possible supports is not, however, limited to this list.
It has now been found that sulfur components, such as H2SO4, SO2, SO3, H2S or COS, act as catalyst poisons. These sulfur components are gradually deposited slowly over the entire catalyst. The catalytic activity is reduced as a result. This reduced activity is unacceptable for use on a large industrial scale. The loss in activity of the catalyst can be permanent or temporary and reversible or irreversible. A further reason for the loss in activity is that most Deacon catalysts are thiophilic and therefore form more or less stable compounds with the sulfur even under very clean conditions thus rendering the catalytically active component inaccessible or deactivating it. For an optimum operation of the Deacon process, the lowest possible content of sulfur components in the HCl gas is therefore necessary.
In most processes, such as the preparation of isocyanates by phosgenation, however, considerable amount of sulfur components can be contained as an impurity in the HCl waste gas and introduced into the Deacon process. The sulfur components can have their origin in the natural gas/coal employed for the preparation of phosgene, i.e., introduction of the sulfur components into the Deacon process can take place via the CO quality in the preparation of phosgene and subsequently via the HCl process gas of the isocyanate installation. Further sources of sulfur can be present in the isocyanate process and pollute the HCl gas stream for the HCl oxidation. These additional sources of sulfur could have their origin in additives used in the isocyanate process (e.g., in the distillation), in the quality of the catalysts used (e.g., for the preparation and destruction of phosgene), and in the purity of the solvents used.
Since even the smallest amounts of sulfur can damage the Deacon catalyst reversibly or irreversibly, an expensive and comprehensive purification of the gas is to be undertaken before the isocyanate process gas comes into contact with the Deacon catalyst. This purification of the educts before they enter into the Deacon reactor is therefore essential for the life of the catalyst and accordingly for the profitability of the preparation of chlorine from HCl by catalytic oxidation.
EP 0 478 744 describes the adsorptive removal of SO2 from waste gases. A purification of an HCl stream for use in a Deacon process is not described here.
JP 2005-177614 describes the removal of sulfur components from gas containing HCl or Cl2. The removal is effected by bringing these gases into contact with metals or compounds thereof. The metals are chosen from groups 8-10 of the Periodic Table of the Elements.

This patent is subject to a terminal disclaimer.

Process for the oxidation of a gas mixture containing hydrogen chloride


A power contact electrode plasma therapy circuit includes a pair of terminals adapted to be connected to a set of switchable contact electrodes of a power contact. A plasma ignition detector is configured to detect an electrical parameter over the switchable contact electrodes indicative of the formation of plasma between the switchable contact electrodes and output a plasma ignition signal based on the electrical parameter as detected. A plasma burn memory is configured to receive and store the plasma ignition signal. A controller circuit is configured to receive from the plasma burn memory the plasma ignition signal, start a time based on receipt of the plasma ignition signal, and upon the timer meeting a time requirement, output a plasma extinguish command. A plasma extinguishing circuit, configured to bypass the pair of terminals upon receiving the trigger signal to extinguish the plasma between the switchable contact electrodes.

Product designers, technicians, and engineers are trained to accept manufacturer specifications when selecting electromechanical relays and contactors. None of these specifications, however, indicate the serious impact of electrical contact arcing on the life expectancy of the relay or the contactor. This is especially true in high-power (e.g., over two (2) Amperes) applications.
Electrical current contact arcing may have a deleterious effect on electrical contact surfaces, such as relays and certain switches. Arcing may degrade and ultimately destroy the contact surface over time and may result in premature component failure, lower quality performance, and relatively frequent preventative maintenance needs. Additionally, arcing in relays, switches, and the like may result in the generation of electromagnetic interference (EMI) emissions. Electrical current contact arcing may occur both in alternating current (AC) power and in direct current (DC) power across the fields of consumer, commercial, industrial, automotive, and military applications. Electrical current contact arcing can result in atomic recombination of the power contact electrodes, molecular disassociation, evaporation and condensation, explosion and expulsion of material, forging and welding of the power contact electrodes, fretting and fitting of the power contact electrodes, heating and cooling, liquefication and solidification of material, and sputtering and deposition processes.

Power contact electrode surface plasma therapy


A device and method for braiding hair or other flexible filaments is disclosed herein. The device comprises a set of gears comprising sector gears and elliptical gears, the elliptical gears having a hollow center portion for receiving the hair or other flexible material. The device further comprises a controller, a motor, a power source, and a user interface. The user interface allows the user to select a variety of weaving patterns. The device and method of the present disclosure may be employed to weave four or more strands of material into a braid.

Braiding is widely recognized as a form of hairstyling, and is commonly used to form ropes and other objects. Numerous devices have been developed to assist in braiding or intertwining hair and other materials. These devices are often directed to braiding hair in a flat, three-strand pattern. For example, U.S. Pat. No. 4,369,690 discloses a hand held, hand operated device with a set of three elliptical gears, through which the user places his or her hair. By using a rack and pinion connected to a hand crank, two sector gears move the elliptical gears in an alternating pattern, thus forming the braid. Other hair-braiding devices, such as disclosed in U.S. Pat. No. 5,988,181, use motors or actuators to move strands about in a set pattern to result in a three-strand braid.
Existing hair braiding devices, however, exhibit several drawbacks, including disorderly braids, inconsistent performance, and/or difficult operation. Further, the existing devices are limited to repeating a single braiding pattern using three strands.


An image forming apparatus wherein a latent image is electrostatically formed on a surface of a photosensitive member and developed by a developing device. In the above image forming apparatus, the reference line image is formed on the surface of the photosensitive member outside the effective image forming area. The width of the reference line image is detected by a sensor. A developing bias voltage applied to the developing device is controllably changed based on the result of detection by a sensor.

1. FIELD OF THE INVENTION
The present invention relates to an image forming apparatus for printing and copying apparatus using electrophotographic processes.
2. DESCRIPTION OF THE RELATED ART
Conventional image forming apparatus for printers and the like control the amount of toner supplied to the developing devices to maintain a constant toner density within the developing material, and adjust the electric charging potential and developing bias voltage so as to maintain image quality, particularly uniform image density. Due to the aforesaid type of image density control, a reference electrostatic latent image pattern is formed outside of the effective image formation region on the surface of the photosensitive drum for the purpose of density detection, said reference latent image pattern is developed to produce a visible toner image of the reference latent image, i.e., a reference density pattern image. The density of the reference density pattern image is detected by means of a density detecting sensor of a reflecting type comprising a photoemitter element and a photoreceptor element, such that the amount of toner supplied to the developing devices can be controlled in accordance with the aforesaid reference density detection.
Conventional methods, however, use only the image density criterium in maintaining uniform image quality, and do not consider image resolution. Conventional methods, therefore, do not resolve the problem that line images, e.g., characters and lines and the like become thinner and thicker due to the effects of photosensitive drum deterioration and the like.

Laser beam printer capable of forming line images having stable image width


Described systems and methods enable protecting client devices (e.g., personal computers and IoT devices) implementing encrypted DNS protocols against harmful or inappropriate Internet content. A DNS proxy intercepts an attempt to establish an encrypted communication session between a client device and a DNS server. Without decrypting any communications, some embodiments of the DNS proxy determine an identifier of the respective session and an identifier of the client device, and send a query tracer connecting the session identifier with the client identifier to a security server. In some embodiments, the security server obtains the domain name included in an encrypted DNS query from the DNS server and instructs the DNS server to allow or block access of the client device to the respective Internet domain according to a device- and/or user-specific access policy.

The invention relates to computer security, and in particular to protecting users from malicious Internet content.
Malicious software, also known as malware, affects a great number of computer systems worldwide. In its many forms such as computer viruses, Trojan horses, spyware, and ransomware, malware presents a serious risk to millions of computer users, making them vulnerable to loss of data and sensitive information, to identity theft, and to loss of productivity, among others. An important avenue for malware proliferation consists of users inadvertently accessing websites hosting malicious or fraudulent content.
Meanwhile, an increasing number of devices informally referred to as the Internet of Things (IoT) are being connected to communication networks and the Internet. Such devices include, among others, smartphones, smartwatches, TVs and other multimedia devices, game consoles, home appliances, and various home sensors such as thermostats. As more such devices go online, they become exposed to security threats like malware and intrusion. Therefore, there is an increasing need of securing such devices against malware, as well as of protecting communications to and from such devices. A particular area wherein interest has been renewed by the advent of the Internet of Things includes access control applications, for instance parental control and preventing confidential information from being transmitted via IoT devices.
Conventional methods of protecting users and devices include intercepting a domain name service (DNS) message sent by a protected device during an attempt to connect to a remote Internet resource. In one such example, a modified DNS server may look up the requested domain in a blacklist. When the domain is considered unsafe, the DNS server may block access and/or redirect the respective request to a replacement IP address serving a warning message. In another example, such DNS-based traffic filtering is performed by hardware and/or software components executing on a user's network appliance (e.g., gateway or router).
Concerns for user privacy have led to the development of encrypted domain name services. Examples include DNS over transport layer security (TLS), as described for instance in request for comments (RFC) 7858 of the Internet Engineering Task Force (IETF), and DNS over hypertext transport protocol secure (HTTPS), as described for instance in IETF RFC 8484. Since such protocols implement end-to-end encryption, they may substantially hinder computer security activities by preventing an intermediary (e.g., router) from carrying out DNS-based traffic filtering.
There is therefore considerable interest in developing computer security systems and methods enabling traffic filtering in the case of encrypted DNS.

Systems and methods of controlling internet access using encrypted DNS


A method for generating a calibrated parallel magnetic resonance image is provided in a manifestation of the invention. A magnetic resonance imaging excitation is applied. A plurality of echoes at different echo times (TE) is acquired. The acquired plurality of echoes from different echo times is used to create a chemical shift corrected calibration map.

This invention relates generally to magnetic resonance imaging, and more particularly the invention relates to species imaging in the presence of magnetic field heterogeneity.
Reliable and uniform fat suppression is essential for accurate diagnoses in many areas of MRI. This is particularly true for sequences such as fast spin-echo (FSE), steady-state free precession (SSFP) and gradient echo (GRE) imaging, in which fat is bright and may obscure underline pathology. Although conventional fat saturation may be adequate for areas of the body with relative homogeneous Bo field, there may be many applications in which fat saturation routinely fails. This is particularly true for extremity imaging, off-isocenter imaging, large field of view (FOV) imaging, and challenging areas such as the brachial plexus and skull based, as well as many others. Short-TI inversion recovery (STIR) imaging provides uniform fat suppression, but at a cost of reduced signal-to-noise ratio (SNR) and mixed contrast that is dependent on T1. This latter disadvantage limits STIR imaging to T2 weighted (T2W) applications, such that current T1 weighted (T1W) applications rely solely on conventional fat-saturation methods. Another fat suppression technique is the use of spectral-spatial or water selective pulses; however, this method is also sensitive to field inhomogeneities.
"In and Out of Phase" Imaging was first described by Dixon in "Simple Proton Spectroscopic Imaging", Radiology (1984) 153:189-194, and was used to exploit the difference in chemical shifts between water and fat and in order to separate water and fat into separate images. Glover et al. further refined this approach, described in Glover G., "Multipoint Dixon Technique for Water and Fat Proton and Susceptibility Imaging", Journal of Magnetic Resonance Imaging (1991) 1:521-530, with a 3-point method that accounts for magnetic field inhomogeneities created by susceptibility differences. This method was applied with FSE imaging by acquiring three images with the readout centered at the spin-echo for one image and symmetrically before and after the spin-echo in the subsequent two images.
Such multiecho imaging may use parallel imaging to increase scanning speed. Parallel imaging requires precise knowledge of spatial distribution of the sensitivity array of RF coils.

Calibration maps for parallel imaging free of chemical shift artifact

The Board of Trustees of the Leland Stanford Junior University


A pneumatic tire adapted to effectively suppress temperature rise of a tread portion during loaded rolling of the tire, and sufficiently suppress failure of the tread portion due to the temperature rise. The tread portion of the pneumatic tire extends between both tread ends and has a tread surface with lug grooves. Each lug groove extends in a tire width direction and has an opening at its one end to a buttress that extends from the tread end radially inwards of the tire. The buttress has a surface with a projection on one side, in a tire circumferential direction, of the buttress-side opening of the lug groove to protrude in the tire width direction. The projection has a radially outer end in a radially outer side than a radially inner end of the buttress-side opening of the lug groove.

In pneumatic tires for heavy load vehicles, in order to preserve the traction performance of the tire, the tread surface of the tread portion situated between both tread ends is conventionally formed with lug grooves extending in the tire width direction such that at least one end of the lug groove opens in the tread end.
Pneumatic tires for heavy load vehicles are known, wherein the traction performance is preserved by forming lug grooves in the tread surface so that one end of the lug groove opens in the tread end on one side in the tire width direction and the other end terminates at a location between the both tread ends. For such tires, there has been proposed to improve the anti-cut/separation property of the tire by forming sipes that are deeper than the lug groove and thereby achieving a communication, in the tire width direction, of a lug groove that opens at the tread end on one side in the tire width direction, with a lug groove that opens at the tread end on the other side in the tire width direction (refer, for example, to Patent Document 1). Here, the term "cut/separation" refers to separation of the tread rubber that occurs along the outer peripheral surface of the belt when the widthwise center region of the tread portion (hereinafter referred to as "the tread center region") is subjected to deep injury that reaches as far as the belt.
Moreover, in the above-mentioned conventional pneumatic tires for heavy load vehicles wherein the lug groove on one side in the tire width direction is communicated by a sipe with the lug groove on the other side in the tire width direction, it is possible to suppress the shearing deformation of the tread rubber situated on the stepping-in side during the loaded rolling of the tire and thereby improve the anti-cut/separation property of the tire, by arranging sipes that are deeper than the lug groove.


A system and method for controlling a camera assembly may include monitoring an image field for blinks by one or more subjects in the image field. The monitoring may be carried out by generating a video signal of the image field, the video signal having a sequence of frames; subtracting a previous frame of the video signal from a current frame of the video signal to generate a difference frame; and identifying image data in the difference frame that is representative of a blink. Each blink may be tracked and associated with a subject from the one or more subjects. Statistical data regarding blink duration and blink rate for each subject from the one or more subjects may be generated. In response to user input to command the taking of a photograph, a determination if a blink is in progress may be made and a flash of the camera assembly may be fired and image data for the photograph may be captured if no blink is detected at the time of the command. Otherwise, firing of the flash and the capturing of the image data may be delayed by an amount of time that is based on the statistical data to minimize firing the flash and capturing the image data during a blink of the one or more subjects.

Mobile and/or wireless electronic devices are becoming increasingly popular. For example, mobile telephones, portable media players and portable gaming devices are now in wide-spread use. In addition, the features associated with certain types of electronic devices have become increasingly diverse. For example, many mobile telephones now include cameras that are capable of capturing still images and video images.
In low light situations, many cameras rely on a flash to provide supplemental light to the scene to improve the image quality of a resultant photograph. But if the flash is fired and image data for the photograph is captured while a person in the image field is blinking, then the resultant representation of the subject in the photograph will appear with his or her eye shut or partially shut.

Camera system and method for operating a camera system


A magneto-optical disk including a transparent substrate, pit strings containing information formed in spiral or concentric form on a surface of the transparent substrate, a magneto-optical recording medium layer for covering the surface of the transparent substrate having the pit strings formed thereon, and magneto-optical recording areas formed by spiral or concentric flat portions between adjacent pit strings. An optical pickup for reproducing pit information and magneto-optically-recorded information from the magneto-optical disk. A magneto-optical disk drive for recording and reproducing information on the magneto-optical disk. The magneto-optical disk has a memory capacity which is twice the memory capacity of a conventional magneto-optical disk having ROM, and is accessed at high speeds.

Optical disk memory as high-density and high-capacity memory, such as a read-only CD (compact disk) and a magneto-optical disk which allows information recorded thereon to be rewritten, has already been on the market.
As illustrated in FIG. 9, read-only memory has minute pits 42 as permanent information created in spiral form on one of the surfaces of a transparent substrate 41 such PC (polycarbonate) and PMMA (acrylic) substrates. Such a disk having the pits allows the mass production of the same information.
On the other hand, as illustrated in FIG. 10, a magneto-optical disk has spiral guide grooves 52 on one of the surface of a transparent substrate 51, and a recording medium designed for use with a magneto-optical disk on the surface of the transparent substrate 51 whereupon the guide grooves 52 are formed. With this magneto-optical disk, signals are recorded on and reproduced from the recording medium. The location on which signals are to be recorded is either on the guide grooves 52 or lands 53 between the guide grooves 52 (if the width of the land 53 is larger than that of the guide groove 52 as shown in FIG. 10, signals are usually recorded on the lands 53). Since the recording medium is a film of a magnetic substance, it is possible to erase the recorded information and to record new information over the erased information. This is a significant characteristic of a magneto-optical disk.
A magneto-optical disk having both the characteristics of the rewritable disk and the disk containing only the permanent information is proposed. Such a disk with ROM (read-only memory) is divided into zones at a predetermined radius of the disk. For example, as illustrated in FIG. 11, a magneto-optical disk is divided into zone A where the permanent information is recorded in the form of pits and zone B where guide grooves are formed and rewritable information is recorded.
However, with the structure of the conventional magneto-optical disk with ROM, the ROM area where the permanent information is recorded and the magneto-optical memory area where information is rewritable are merely provided. Therefore, the volume of information recorded on the disk remains the same. Moreover, when reading the permanent information recorded in the ROM area and recording new information in the magneto-optical area according to the content of the information, it is necessary to move a light beam from the inner zone A toward the outer zone B.
In order to reproduce signal from an optical disk, generally, an optical pickup is required. As illustrated in FIG. 12, the optical pickup includes lens systems 72 and 77 for converging light 78 from a light source 71 such as a semiconductor laser, a photodetector 75 for reading information signals, a beam splitter 73 for directing reflected light from the disk to the photodetector 75, and a lens 74.
With this structure, however, since the weight of the optical pickup is increased, it takes at least several tens ms to move the optical pickup from the center portion of the optical disk toward the outer portion, resulting a linger access time to the information.
In short, the structure of the conventional magneto-optical disk with ROM suffers from the following drawbacks: the volume of information recorded on a single disk is the same as that recorded on a disk having only the ROM area or disk having only the magneto-optical area; and it takes a long time to access to the ROM area and the magneto-optical area by turns.

Magneto-optical disk, optical pickup, and magneto-optical disk drive


Aspects of the present disclosure relate to data cache management. In embodiments, a storage array's memory is provisioned with cache memory, wherein the cache memory includes one or more sets of distinctly sized cache slots. Additionally, a logical storage volume (LSV) is established with at least one logical block address (LBA) group. Further, at least one of the LSV's LBA groups is associated with two or more distinctly sized cache slots based on an input/output (IO) workload received by the storage array.

A storage array is a data storage system that includes multiple storage drives (e.g., hard disk drives (HDDs), solid-state drives (SSDs)), and memory such as random-access memory (RAM) or dynamic RAM (DRAM). Storage array system allows the separation of data storage from computing devices. The break of data storage from computing devices enables multiple users to collaborate and share information in a scalable manner. A storage array can include a storage and memory management system that controls data storage and access to the array's storage drives and memory. In addition, the storage and memory management system can have an operating system that manages a storage array's memory, processes, software, hardware, and communications.

Cache memory architecture and management


The object of the invention is to provide a semiconductor device that can form photodiodes that do not short circuit, without damage that causes leakage, despite formation of the opening part, and its manufacturing method. The second semiconductor layer (12, 16) of the second conductivity type is formed on the main surface of the first semiconductor layer (10, 11) of the first conductivity type. Element-separating regions (13, 14, 15, 17) formed at least on the second semiconductor layer separate the device into the regions of plural photodiodes (PD1-PD4). Conductive layer 18 is formed on the second semiconductor layer 16 in a pattern that is divided for each of the photodiodes and is connected to the second semiconductor layer 16 along the outer periphery with respect to all of the plural photodiodes. Insulation layer (19, 21) is formed on the entire surface to cover conductive layer 18. An opening part, which reaches the second semiconductor layer 16, is formed in the insulation layer (19, 21) in the region inside the pattern of conductive layer 18.

Photodiodes generate current after receiving light. They are widely used as light-receiving elements for optical pickup devices incorporated into optical disc devices, such as CD or DVD devices. A photodiode is constituted by a semiconductor with pn junctions. A reverse bias is applied to the pn junction to widen the depletion layer, and a high electric field is applied. Electron-hole pairs are generated by the absorbed light in the depletion layer. Under the attraction of the electric field, the electrons move to the n-type semiconductor region, while the holes move to the p−-type semiconductor region to form a current.
Types of photodiodes include PIN photodiodes, which have a p−-layer or n−-layer or other intrinsic layer (referred to as Layer I hereinafter) containing electroconductive impurity at low concentration between the p layer and n layer and can easily widen the depletion layer at a low voltage, and avalanche photodiode having a region where avalanche decay occurs.
Japanese Kokai Patent Application No. 2001-320079 discloses a photodiode manufacturing method that can be used to remove the insulation film on the top layer of the diode without having film peel-off or leakage.
The photodiode formed by the aforementioned method is shown in FIG. 26(A), which is a plan view, and FIG. 26(B), which is the cross-sectional view shown in FIG. 26(A).
For example, p−-type epitaxial layer 101 is formed as Layer I on p++-type silicon semiconductor substrate 100, and n-type epitaxial layer 102 is formed on it to form a pn junction. Also, n+-type semiconductor region 103 is formed in the surface layer part of n-type epitaxial layer 102 in the PIN photodiode region. Silicon nitride layer 103a is formed on the surface in the central part of n+-type semiconductor region 103. Silicide layer 103b made of platinum silicide, etc., is formed near the edge of n+-type semiconductor region 103 in the outer periphery of silicon nitride layer 103a. Silicon nitride layer 103a and silicide layer 103b have a film thickness of, for example, 30 nm. Also, LOCOS element-separating insulation film 104 is formed to surround PIN photodiode region.
A ring-shaped mask layer 105 made of a metal layer is formed from n+-type semiconductor region 103 in the outer periphery of the PIN photodiode to element-separating insulation film 104, and an interlayer insulation film 106 is formed on the mask layer. An opening part H is formed on interlayer insulation film 106 along the inner periphery of metal layer 105 to expose the surface of silicon nitride layer 103a and silicide layer 103b on n+-type semiconductor region 103 in the photodiode region. A surface protective layer 108 is formed to cover opening part H.
In this way, a PIN photodiode PD with the aforementioned configuration is formed.
In the PIN photodiode with the aforementioned configuration, when a reverse bias is applied to n+-type semiconductor region 103 and p− type epitaxial layer 101, the depletion layer is widened from the pn junction surface. When light is incident on the formed depletion layer, electron hole pairs are generated, and optical signals are obtained.
In this case, mask layer 105 is connected to n+ semiconductor region 103, and voltage can be applied to n+-type semiconductor region 103 via mask layer 105.
In the following, the method of forming the aforementioned PIN photodiode PD will be explained.
As shown in the FIG. 27(A) and FIG. 27(B), p-type epitaxial layer 101 and n-type epitaxial layer 102 as Layer I are formed on p++-type silicon semiconductor substrate 100, and element separation is performed using LOCOS element-separating insulation film 104, etc., n+-type semiconductor region 103 is formed by means of ion injection in the surface layer part of n-type epitaxial layer 102 in the PIN photodiode region separated by LOCOS element-separating insulation film 104. Also, silicon nitride layer 103a with a thickness of about 30 nm is formed on the surface in the central part of n+-type semiconductor region 103. With silicon nitride layer 103a having silicide masking function used as a mask, silicide layer 103b made of platinum silicide, etc., and having a thickness of about 30 nm is formed on the surface near the edge of n+-type semiconductor region 103 in the outer periphery of silicon nitride layer 103a.
Then, a metal layer made of TiW, etc., is deposited in a thickness of 200-300 nm by means of sputtering, followed by patterning to form mask layer 105 that covers n+-type semiconductor region 103 and is extended all the way to LOCOS element-separating insulation film 104.
Then, insulation film 106 is formed on the entire surface of mask layer 105. In this case, insulation film 106 is formed by laminating plural layers by depositing silicon oxide by CVD with TEOS used as the raw material, or by depositing a BPSG film, or by depositing silicon nitride via CVD.
Then, as shown FIG. 28(A) and FIG. 28(B), a resist film 107 with a pattern that opens the photosensitive region of the photodiode is formed on insulation film 106. After that, dry etching, such as RIE (reactive ion etching), is performed with mask layer 105 serving as the etching stopper to eliminate the insulation film 106 on the aforementioned photosensitive region to form opening part H.
Then, as shown in FIG. 29(A) and FIG. 29(B), mask layer 105 in the area exposed in opening part H is removed selectively with respect to n+-type semiconductor region 103 and insulation film 106 by means of wet etching to expose n+-type semiconductor region 103.
Then, surface protective layer 108 is formed on the entire surface to obtain the semiconductor device having the PIN photodiode shown in FIG. 26(A) and FIG. 26(B).
In the method of manufacturing a semiconductor device having the aforementioned PIN photodiode, when removing the insulation film 106 from the diode, since mask layer 105 serves as an etching stopper, even if dry etching is used so that no hollow parts are formed on the inner wall surface of opening part H to cause film peeling, no damage that could allow leakage will be caused because the silicon substrate is protected by mask layer 105 in that step.
Also, when eliminating mask layer 105 exposed in the aforementioned opening part H, even if wet etching is used to avoid damage to the silicon substrate, mask layer 105 can be removed selectively without forming hollow parts on the inner wall surface of opening part H of insulation film 106.
However, when the aforementioned photodiode is used as a light-receiving element for an optical pickup device incorporated into a CD, DVD, or other optical disc device, in order to obtain the tracking error signal or focus error signal from the signal fed back from the optical disc, it is necessary to use PDIC formed by combining plural photodiodes.
FIG. 30 is the plan view of a PDIC formed by combining, for example, 4 PIN photodiodes. This figure shows how laser spot S, which is the signal fed back from the optical disc, is incident to the four PIN photodiodes PD1-4.
In this case, laser spot S is incident to target the center of the four PIN photodiodes PD1-4. However, since the part in the intervals between the four PIN photodiodes PD1-4 becomes a dead area, it is desirable to reduce the intervals between the four PIN photodiodes PD1-4 to, for example, 5 μm or less in order to increase the sensitivity.
FIG. 31 is a plan view illustrating the light-receiving surfaces of the photodiodes when the method described in the above-referenced Japanese patent application is applied to the four PIN photodiodes PD1-4 with the intervals reduced to about 5 μm as described above.
The four PIN photodiodes PD1-4 are covered by a common mask layer 110. After the opening part is formed in the insulation film, the mask layer in the opening part is removed. In this case, however, mask layer 110, which is a common conductive layer, is connected to the n+-type semiconductor region equivalent to the light-receiving surface of each of the four PIN photodiodes PD1-4. As a result, a short circuit between the diodes becomes a problem.
FIG. 32 is a plan view illustrating the light-receiving surface of a photodiode in the case when the mask layers are formed independently, and the four PIN photodiodes PD1-4 with an opening part formed in each of them can be laid out as close to each other as possible.
Independent mask layers (111-114) are formed with respect to the four PIN photodiodes PD1-4, respectively.
In this layout, however, the intervals between the four PIN photodiodes PD1-4 are increased to 20 μm, making it difficult to use them as the light-receiving element of an optical pickup device.

Semiconductor device and its manufacturing method


A system for improving the efficiency of drive-through delivery systems is provided. The system can provide complete error tracking and feedback; however, partial or no error tracking and/or feedback can be provided if desired. Errors in order fulfillment can be reduced. Detailed information on product weight and delivery timing can be provided. By analyzing the weight distributions of each food item or any other suitable measurements, production quality and consistency may be monitored. By analyzing the delivery times for each food item type or any other suitable measurements, production efficiency and restaurant work flow may be measured.

The drive-thru window is ubiquitous among fast food restaurants. One frequent problem with this system is the customer receiving an incorrect order. If the customer drives off before fully checking the order, it is frustrating and time-consuming to return and have it corrected. If the customer stays at the drive-thru window long enough to completely check all received items, everyone else in line must wait, significantly reducing overall throughput. Frequent errors in received items can result in lost customers.
Much has been done to optimize the drive-thru system, and in particular to improve accuracy. Many restaurants now include an outdoor display to show the order as entered by the cashier—this way the customer can verify that the order was entered correctly. This does help reduce one error mechanism—incorrect order entry—but doesn't help if the cashier bags the order incorrectly, or if items were wrapped incorrectly. Some restaurants have automatic drink machines. These fully automatic machines handle all drinks associated with an order, reducing the chance of error, but only for drinks. Drive-thru systems have been rearranged to include two windows—a cashier at one window, and a food delivery person at a second window. This improves throughput, and also reduces errors by reducing the number of disparate tasks each worker must perform. The cashier function is even being outsourced to off-site locations, where orders may be received without distractions from the restaurant operations. This results in improved order-taking accuracy, but still does not fully address mistakes in bagging the order and delivering it to the customer.
Another problem with incorrectly assembled and delivered drive-thru orders is the lack of accountability. With the current system, if a customer returns due to an incorrect order, there is no mechanism to track what the error was, or who was responsible.

Method and apparatus for a drive-thru product delivery verifier


Derivatives of mDIVI-1 may be used to target and eliminate cancer stem cells. Disruption in the mitochondrial dynamics balance plays a role in cancer. Proteins involved in regulating mitochondrial dynamics represent potential targets for cancer treatment. Mitochondrial fission protein DRP1 is such a target. Derivatives of mDIVI-1 inhibit DRP1, and have demonstrated inhibition of tumorsphere forming capacity, migration and stemness-related signaling in breast cancer cells. These properties result from induction of mitochondrial oxidative stress and reduction of mitochondrial metabolism in the target cancer cells. The potency of an mDIVI-1 derivative may be dramatically increased through addition of at least one membrane-targeting signal and/or a mitochondria-targeting signal.

Researchers have struggled to develop new anti-cancer treatments. Conventional cancer therapies (e.g. irradiation, alkylating agents such as cyclophosphamide, and anti-metabolites such as 5-Fluorouracil) have attempted to selectively detect and eradicate fast-growing cancer cells by interfering with cellular mechanisms involved in cell growth and DNA replication. Other cancer therapies have used immunotherapies that selectively bind mutant tumor antigens on fast-growing cancer cells (e.g., monoclonal antibodies). Unfortunately, tumors often recur following these therapies at the same or different site(s), indicating that not all cancer cells have been eradicated. Relapse may be due to insufficient chemotherapeutic dosage and/or emergence of cancer clones resistant to therapy. Hence, novel cancer treatment strategies are needed.
Advances in mutational analysis have allowed in-depth study of the genetic mutations that occur during cancer development. Despite having knowledge of the genomic landscape, modern oncology has had difficulty with identifying primary driver mutations across cancer subtypes. The harsh reality appears to be that each patient's tumor is unique, and a single tumor may contain multiple divergent clone cells. What is needed, then, is a new approach that emphasizes commonalities between different cancer types. Targeting the metabolic differences between tumor and normal cells holds promise as a novel cancer treatment strategy. An analysis of transcriptional profiling data from human breast cancer samples revealed more than 95 elevated mRNA transcripts associated with mitochondrial biogenesis and/or mitochondrial translation. Sotgia et al., Cell Cycle, 11(23):4390-4401 (2012). Additionally, more than 35 of the 95 upregulated mRNAs encode mitochondrial ribosomal proteins (MRPs). Proteomic analysis of human breast cancer stem cells likewise revealed the significant overexpression of several mitoribosomal proteins as well as other proteins associated with mitochondrial biogenesis. Lamb et al., Oncotarget, 5(22):11029-11037 (2014).
Mitochondria are extremely dynamic organelles in constant division, elongation and connection to each other to form tubular networks or fragmented granules in order to satisfy the requirements of the cell and adapt to the cellular microenvironment. The balance of mitochondrial fusion and fission dictates the morphology, abundance, function and spatial distribution of mitochondria, therefore influencing a plethora of mitochondrial-dependent vital biological processes such as ATP production, mitophagy, apoptosis, and calcium homeostasis. In turn, mitochondrial dynamics can be regulated by mitochondrial metabolism, respiration and oxidative stress. Thus, it is not surprising that an imbalance of fission and fusion activities has a negative impact on several pathological conditions, including cancer. Cancer cells often exhibit fragmented mitochondria, and enhanced fission or reduced fusion is often associated with cancer, although a comprehensive mechanistic understanding on how mitochondrial dynamics affects tumorigenesis is still needed.
Functional inhibition of mitochondrial biogenesis using the off-target effects of certain bacteriostatic antibiotics or OXPHOS inhibitors provides additional evidence that functional mitochondria are required for the propagation of cancer stem cells. The inventors recently showed that a mitochondrial fluorescent dye (MitoTracker) could be effectively used for the enrichment and purification of cancer stem-like cells from a heterogeneous population of living cells. Farnie et al., Oncotarget, 6:30272-30486 (2015). Cancer cells with the highest mitochondrial mass had the strongest functional ability to undergo anchorage-independent growth, a characteristic normally associated with metastatic potential. The 'Mito-high' cell sub-population also had the highest tumor-initiating activity in vivo, as shown using pre-clinical models. The inventors also demonstrated that several classes of non-toxic antibiotics could be used to halt cancer stem cell propagation. Lamb et al., Oncotarget, 6:4569-4584 (2015). Because of the conserved evolutionary similarities between aerobic bacteria and mitochondria, certain classes of antibiotics or compounds having antibiotic activity can inhibit mitochondrial protein translation as an off-target side-effect.
A master regulator of the mitochondrial fission machinery is the cytoplasmic dynamin-related protein 1 (DRP1, also known as DNM1L). During mitochondrial fission DRP1 is recruited to the mitochondria and interacts with the outer mitochondrial membrane receptors. Subsequently, DRP1 polimerizes and promotes mitochondrial constriction and fission, activities that are fueled by its GTPase activity.

Targeting mitochondrial fission through mDIVI-1 derivatives


A method of the preparation and utilization of polymerized alpha-hydroxycarboxylic-acid-coated proppants for gravel pack and removal of filter cake that was deposited by reservoir drilling fluid. In a preferred example, polyglycolic-acid-coated sand is used to replace conventional gravel pack sand typically used for gravel packing. Under downhole conditions, the acidic by-product generated from the hydration of polyglycolic-acid-coated sand can break down acid-soluble and/or acid-breakable components embedded in the filter cake. This reaction enhances the filter cake removal and the flow of hydrocarbon from the producing formation. The polyglycolic-acid-coated sand may be produced by polymerizing a glycolic acid with a natural or synthetic proppant like 20–40 mesh commercial sand, at temperatures of about 210° F. or higher.

To produce oil and gas from hydrocarbon reservoir, a borehole of tapered and often times deviated geometry is first drilled through geological formations. The hydrocarbon-bearing formation then is drilled with a specially designed reservoir drilling fluid, which may comprise various additives, such as starches and calcium carbonate, that are soluble or breakable by acid, oxidizers, or enzymes, or a combination of these chemicals.
Once the desired borehole in the hydrocarbon reservoir is drilled, production tubes and/or screens are run to the bottom of the borehole and placed against the desired formations for hydrocarbon production. Often times, especially when the hydrocarbon-bearing formations consist of poorly cemented sands, some kind of sand control methods or devices are used to prevent sand particles from the formation from entering and plugging up the production screens and tubes in order to extend the life of the well.
One of the typical sand control methods is to fill the annular space between the wellbore and the production screens with specially sized sand, which is usually larger than the formation sand and commonly known as gravel pack sand. The process to place the sized sand behind the production screen is known as a gravel pack operation.
In order to be able to fill the annular space with sand completely and successfully, the hydrocarbon-bearing formation should have been previously covered with a thin layer of firm and impermeable filter cake formed by the reservoir drilling fluid. This thin and impermeable filter cake may prevent the gravel pack fluid from entering the formation, which when occurring at an uncontrollable rate, would result in gravel pack failure.
After the gravel pack sand has been successfully placed, the filter cake existing between the gravel pack sand and the formation needs to be removed before the flow of hydrocarbon is initiated. Without the removal of the filter cake, plugging of the production screen by the filter cake could occur and would result in a production impairment.
To destroy the filter cake that is now behind the gravel pack sand, various chemicals, breakers and mechanical devices have been developed and used. For example, hydrochloric acid is often delivered by a separate operation to soak the gavel pack sand and filter cake with the aid of wash cups. The mechanical wash cups attached to the end of a work string must be picked up at the surface and lowered to the bottom through the inside of the screen. The hydrochloric acid is then pumped through the gravel pack sand repeatedly. The goal of this exercise is to destroy a large amount of the acid-soluble and acid-breakable components in the filter cake.
Other breakers, such as oxidizers and enzymes, may also be delivered to destroy oxidizer- and enzyme-breakable organic components, such as starch polymers. However, these breakers are considered less efficient in several ways. First, they are not effective in destroying acid-soluble and acid-breakable inorganic components in the filter cake, such as calcium carbonate. As a result, acid-soluble and breakable components will remain behind the gravel pack sand and may subsequently cause impairment during the production of the well. Second, many oxidizing breakers have compatibility issues with certain brines. They may react with the brine and create undesirable by-products, such as Cl2 and Br2 gases. This reaction will occur even before the breakers were pumped down to attack the filter cake. Third, in addition to brine compatibility issues, enzyme breakers also have a temperature issue. Most enzyme breakers will lose reactivity in highly concentrated divalent brines, and at temperatures above 200° F.
The above breakers are normally pumped on a separate trip after the gravel pack sand has been set. They are not pumped during the gravel pack operation because they can create precarious conditions for the operation. For instance, the acid-based breakers can destroy the filter cake during gravel pack operation, and consequently result in high fluid loss and premature failure in the gravel pack operation.
Pumping oxidizers and enzyme breakers with gravel pack sand may cause inconsistent application of oxidizers and enzyme breakers to the filter cakes. Since most of the solid oxidizers and enzyme breakers are organic materials with relatively low specific gravity and small particle size, they tend to be pushed toward the screen rather than toward the filter cake where the reaction needs to take place. As a result, the concentration and distribution of these breakers in the gravel pack sand is likely to be erratic, making the filter cake removal less effective.
Microencapsulation is one technique used to deliver wellbore chemicals downhole. The microencapsulation process and application of microencapsulated oil field chemicals, such as scale inhibitors, corrosion inhibitors, surfactants, bactericides, paraffin dispersants, pourpoint modifiers, cement additives, fracture fluid cross linkers, emulsion breaking chemicals, chemical tracers, radioactive tracers, and asphaltene treatment chemicals, using condensation product of hydroxyacetic were disclosed in U.S. Pat. No. 4,986,354. The encapsulated special chemicals are injected along with water into oil wells. Disintegration of the encapsulating polyglycolic polymer in the presence of water allows the encapsulated chemicals to be released to achieve desired reactions.
Microencapsulation of pesticides, insect growth regulators, and other organic compounds in biodegradable polymers from the group consisting of polylactic acid and copolymers of lactic and glycolic acids was disclosed in U.S. Pat. No. 4,272,398.
None of the methods above efficiently deliver the necessary breakers to a filter cake. Thus, there exists an on-going need and desire for breakers which provide a slow release mechanism to initiate the disintegration of filter cakes so that gravel pack operations can be continued.

Acid-coated sand for gravel pack and filter cake clean-up


A flowable, paste-like composition capable of setting in a clinically relevant period of time into an antimicrobial agent loaded apatitic product having sufficient compressive strength to serve as a cancellous bone structural material is provided. The subject compositions are prepared by combining dry ingredients with a physiologically acceptable lubricant and an antimicrobial agent, where the dry ingredients comprise at least two different calcium phosphates. The subject compositions find use in a variety of different applications, including orthopaedic, dental and cranio-maxillofacial applications.

Calcium phosphate cements, in which one or more dry components and a liquid are combined to form a flowable, paste-like material that is subsequently capable of setting into a solid calcium phosphate product, hold great promise for use as structural materials in the orthopedic, cranio-maxillofacial, dental and related fields. For example, it is desirable to be able to inject a flowable material into a cancellous bone void and have the material set into a solid calcium phosphate mineral product that is capable of withstanding physiological loads. Materials that set into solid calcium phosphate mineral products are of particular interest as such products can closely resemble the mineral phase of natural bone and are potentially remodelable, making such products extremely attractive for use in orthopedics and related fields.
In view of the great interest in calcium phosphate cements, a variety of different formulations have been developed to date. See the Relevant Literature section infra.
Despite the number of different calcium phosphate cements that have been produced, there is continued interest in the development of new calcium phosphate cements that are particularly suited to a particular type of application. One such cement of interest would be a calcium phosphate cement that produces a flowable material capable of setting into an antimicrobial apatitic product that is suitable for use a cancellous bone structural material.
Relevant Literature
U.S. Pat. No. 5,591,453 describes a silica-based glass carrier for biologically active molecules. Patents of interest describing calcium phosphate cements include: 4,684,673; 5,037,639, 5,683,461; 5,676,976; 5,650,176; 4,108,690 and 5,508,342, as well as 4,880,610; 5,047,031; 5,129,905; 5,336,264; 5,053,212; 5,178,845; 5,580,623; 5,569,442; 5,571,493; 5,496,399; 5,683,667; 5,683,496; and 5,697,981. Also of interest are WO 96/36562 and WO 97/17285.
Constantz et al., "Skeletal Repair by in Situ Formation of the Mineral Phase of Bone," Science (Mar. 24, 1995) 267: 1796-1798, describes a calcium phosphate cement comprising .alpha.-tricalcium phosphate, MCPM, and CaCO.sub.3. Also of interest is: Lemaitre et al., "Setting, Hardening and Resorption of Calcium Phosphate Hydraulic Cements," Rev. Stomatol. Chir. Maxillofac. (1992) 93: 163-165.
Other references of interest include: Takechi et al., "Effects of Added Antibiotics on the Basic Properties of Anti-Washout-Type Fast-Setting Calcium Phosphate Cement," J. Biomed. Mater. Res. (February 1998) 39: 308-316; Bohner et al., "Gentamycin-Loaded Hydraulic Calcium Phosphate Bone Cement as Antibiotic Delivery System," J. Pharm. Sci. (May 1997) 86: 565-572; Hamanishi et al., "A Self-Setting TTCP-DCPD Apatite Cement for Release of Vancomycin," J. Biomed. Mater. Res. (1996) 33: 139-143; Otsuka et al., "A Novel Skeletal Drug Delivery System Using Self-Setting Calcium Phosphate Cement," J. Pharm. Sci. (November 1994) 83: 1569-1573; Otsuka et al., "A Novel Skeletal Drug Delivery System Using Self-Setting Calcium Phosphate Cement," J. Pharm. Sci. (May 1994) 83:611-615; Welch, "Antibiotics in Acrylic Bone Cement," J. Biomed Mater. Res. (1978) 12: 679-700; and Lautenschlager et al., "Mechanical Properties of Bone Cements Containing Large Doses of Antibiotic Powders," J. Biomed. Mater. Res. (November 1976) 10: 929-938.

Calcium phosphate cements comprising antimicrobial agents


Embodiments of the present invention provide a method, apparatus and system for absorbing heat from an active side of a die by a plurality of cold conductive elements embedded in said die, and releasing said absorbed heat by a plurality of hot conductive elements embedded in a substrate connected to said die.

A die, e.g., a semiconductor die, may produce heat during its operation. The heat may be produced by an active side of the die. A cooling device may be used to reduce the temperature of the die during operation, e.g., such that the temperature of the die does not exceed a pre-defined maximum temperature limit.
Conventional cooling devices, for example, a heat sink in contact with a back side of the die and cooled, e.g., by a fan, may be used to reduce the temperature of the active side by removing heat from the backside of the die. In such devices, the location in which the heat is removed, e.g. the backside, is different than the location in which the heat is produced, e.g., the active side. Thus, due to the thermal resistance of the die and/or of any other material layers which may be located between the die and the heat sink, e.g., a Thermal insulating Material (TIM) and/or an Integral Heat Spreader (IHS), the cooling device located on the backside of the die may not efficiently remove the heat produced by the active side. As a result, the temperature of the active side may be higher than ambient temperature.
Some cooling devices implement a Thermo-Electric Converter (TEC) located relatively close to the active side of the die, e.g., connected to the die or to a substrate connected to the die, which is connected to the active side of the die. The TEC may have a cold section and a hot section. The cold section may absorb the heat produced by the active side of the die and the hot section may release the heat. However, the heat released by the hot section may increase the heat of the cold section, since both sections are located either in the substrate or in the die, which have a relatively low thermal resistance. Thus, these devices may not effectively remove the heat produced by the active side.
It will be appreciated that for simplicity and clarity of illustration, elements shown in the figures have not necessarily been drawn to scale. For example, the dimensions of some of the elements may be exaggerated relative to other elements for clarity. Further, where considered appropriate, reference numerals may be repeated among the figures to indicate corresponding or analogous elements.

Method and apparatus for thermo-electric cooling


Novel derivatives of phencyclidine are provided as precursors for conjugating to antigenic proteins for the preparation of antibodies which bind to phencyclidine or conjugation to enzymes for use as reagents in immunoassays. The combination of the antibodies and enzyme conjugates provide a sensitive and rapid assay for phencyclidine.

1. Field of the Invention
The present invention is directed to novel phencyclidine compounds and conjugates of these compounds to proteins.
2. Discussion of the Background
1-(1'-phenylcyclohexyl)piperidine, otherwise known as phencyclidine, PCP, was originally used as an analgesic anaesthetic drug (pain-killing) for humans. It is now legally used exclusively as an animal tranquilizer due to its strong side effects, such as euphoria and hallucinations. Probably because of these side effects, PCP has become prevalent in the illicit drug market. It is often sold as "peace pill", "angel dust", "dust", "crystal", or "supergrass".
PCP is a dangerous and potent drug with lethal potential and has become a major drug abuse problem. Thus it is desirable that there be a simple accurate rapid technique for detecting the presence of PCP in physiological fluids, such as blood serum, urine and saliva.
There have been difficulties in attempting to identify PCP in physiological fluids. In one investigation (D. C. K. Lin et al., Biochem. Mass Spec., 206 (1975)) of urine from patients intoxicated by PCP, no metabolites were detected in untreated urine. However, two urinary metabolites were freed from conjugates by enzymatic hydrolysis and identified as 4-phenyl-4-piperidinocyclohexanol and 1-(1-phenylcyclohexyl)-4-hydroxypiperidine. An additional metabolite, tentatively identified as 1-phenyl-(4-hydroxycarboxyl)-4-hydroxypiperidine, was found in the urine of the rhesus monkeys after administration of PCP.
U.S. Pat. No. 4,281,065 discloses PCP conjugates to antigenic proteins and to enzymes. The conjugates are formed by bonding poly(amino acids) to the phenyl group of PCP.
U.S. Pat. No. 4,446,065 discloses oxime derivatives of PCP in which the cyclohexyl group of PCP is derivatized. The oxime derivatives are used to form protein conjugates useful in assays for PCP determinations.

Phencyclidine compounds and assays for its determination


Current control circuit controls an output voltage of DC power supply so as to increase current passing through inverter circuit as the motor increases its the speed. The control offers an RPM—torque characteristic of the motor in which torque increases as the RPM increases. By virtue of the RPM—torque characteristic, a ventilating device employing brushless DC motor exhibits preferable air quantity—static pressure characteristic where less change in air quantity is expected even when a pressure loss—outside wind pressure, duct length or the like—varies.

FIG. 14 shows a conventional brushless DC motor, which is disclosed in Japanese Patent Unexamined Publication No. 2003-284307. The motor contains rectifier 101 for rectifying voltage VAC of AC power supply; DC-DC converter 110 for converting rectified DC voltage (√2)·VAC into low DC voltage VM; smoothing capacitors 109, 111; motor stator-coils 103, 104; magnet rotor 105; switching elements 107, 108; Hall element (not shown) for detecting the magnetic pole of the rotor; and control circuit 106. Control circuit 106 rotates the motor by turning on/off switching elements 107, 108 using a signal from the Hall element and, at the same time, controls the characteristics of the motor so as to be suitable for use.

Brushless DC motor and electric apparatus mounting it


A speaker includes a main-cone and a sub-cone. Linear thin portions configured to reduce a plate thickness of the sub-cone are formed on a region containing at least any one of an outer side and an inner side of the sub-cone. Each of the linear thin portions has both of a component in a radial direction and a component in a circumferential direction of the sub-cone. First and second linear thin portions cross each other at an intersection. With this configuration, stiffness of the whole sub-cone is reduced to enhance a divided vibration of the sub-cone. In particular, a vibrational displacement of an outer peripheral portion of the sub-cone, from which a sound is mainly radiated, is increased.

A reproducible frequency band of a cone-type speaker is determined by a diameter of a cone. Therefore, a large-size speaker having a cone diameter of, for example, 10 cm or larger cannot sufficiently reproduce a high-frequency band equal to or higher than 5 kHz in comparison to a low-frequency band.
A double cone speaker is known, in which a sub-cone having a smaller diameter than that of a main-cone is bonded to the main-cone of the speaker. In this manner, the double cone speaker is capable of sufficiently reproducing a sound in a frequency band ranging from the low-frequency band to the high-frequency band. The sub-cone of the double cone speaker radiates a sound through a divided vibration. Therefore, by forming the sub-cone into an easily deformable shape, the reproducible frequency band can be enlarged while an acoustic radiation power can be increased.
In Patent Literature 1, there is described a configuration of a double cone speaker in which a plurality of linear thin portions extending from an outer peripheral portion of a sub-cone toward a central portion are formed. Further, in Patent Literature 2, there is described a configuration in which a wave-shaped corrugation is formed on a sub-cone.


A transcurrent circuit in which a first current flows in an output-stage circuit based on a second current flowing in an input-stage circuit and a given current transform ratio of the first current to the second current. In the transcurrent circuit, at least one of the input-stage circuit and the output-stage circuit in the transcurrent circuit is constructed with a plurality of transistors. Further, all the transistors in both of the input-stage circuit and the output-stage circuit have the same gate length.

1. Field of the Invention
The present invention generally relates to a transcurrent circuit, and more particularly, to a transcurrent circuit forming a part of an electronic circuit generally used in electronic devices.
2. Description of the Related Art
Recently, in integrated circuits (ICs) used for miniaturization and power reduction of electronic devices, particularly, an integrated circuit (IC) manufactured in a process using a Metal Oxide Semiconductor Field Effect Transistor (MOSFET) is widely used. Further, in these electronic circuits constructed with transistors, a transcurrent circuit and a current mirror circuit, which produce a current output determined by a specified transient function from a current input, are known.
When manufacturing the integrated circuit, it is difficult to form each device element at precise absolute characteristic values, but it is significantly easy to precisely determine a relative value between the characteristics of the device elements. Using the above-discussed feature of the integrated circuit, in a transcurrent circuit such as a current mirror circuit, miniaturization of the circuit forming area and reduction of the circuit power consumption are required.
FIG. 1 shows a schematic diagram of a prior art transcurrent circuit. In FIG. 1, a basic circuit of a transcurrent circuit 11 is shown. In the transcurrent circuit 11, a drain of a transistor M1 (for example, an N-channel MOSFET) is connected to a first power source 12, and a source thereof is connected to an earth ground (GND) as a second power source. Further, a gate of the transistor M1 is connected to the drain of itself. The transistor M1 is specified by a ratio of a gate width W.sub.1 to a gate length L.sub.1 (W.sub.1 /L.sub.1).
On the other hand, a drain of a transistor M2 of an N-channel MOSFET is connected to a third power source 13, and a source thereof is connected to the GND. Further, a gate of the transistor M2 is connected to the gate of the transistor M1. The transistor M2 is specified by a ratio of a gate width W.sub.2 to a gate length L.sub.2 (W.sub.2 /L.sub.2).
In this case, the gate width W.sub.2 of the transistor M2 is designed to be the same as the gate width W.sub.1 of the transistor M1, and the gate length L.sub.2 is designed to be the same as n times the gate length L.sub.1 of the transistor M1. Therefore, the ratio (W.sub.2 /L.sub.2) in the transistor M2 is represented by a ratio (W.sub.1 /nL.sub.1).
In the transcurrent circuit 11, when a drain current I.sub.1 flows into the transistor M1 on an input stage, a voltage is applied to the drain of the transistor M2 on an output stage, and a current I.sub.2 as an output current flows through the transistor M2.
FIG. 2A shows a top plane view of a layout pattern of the transistor M1 in the integrated circuit shown in FIG. 1, and FIG. 2B shows a top plane view of a layout pattern of the transistor M2 in the integrated circuit. At the transistor M1 and the transistor M2 shown in FIG. 2A and FIG. 2B, a drain (D) region, a gate (G) region, and a source (S) region are formed on the wafer at a given distance interval.
As discussed above, the gate length and the gate width of the transistor M1 are respectively designed to be L.sub.1 and W.sub.1. For the transistor M2, the gate length and the gate width thereof are designed to be L.sub.2 (=nL.sub.1) and W.sub.2 (=W.sub.1). For the transistors M1, M2, a ratio of current transform (I.sub.2 /I.sub.1) is changed by the gate length and the gate width.
Namely, a current transform ratio R1 (=I.sub.2 /I.sub.1) in the transcurrent circuit 11 is represented by the following equation. ##EQU1##
The above equation is represented using each gate length and each gate width as follows: EQU R1=(W.sub.1 /nL.sub.1).times.(L.sub.1 /W.sub.1)=1/n
For example, for achieving a current ratio I.sub.1 :I.sub.2 =1:2, the gate widths of the transistors M1, M2 are set to be the same and the gate length of the transistor M1 is set to be 2L.sub.1 (namely, n=2).
Since the circuit forming area of the transcurrent circuit needs to be reduced, the gate lengths of the transistors M1, M2 are designed as small as possible, for example, to be less than 1 .mu.m, which is substantially the minimum value with present manufacturing techniques.
FIG. 3 shows a schematic diagram of a current-voltage transforming circuit using the prior art transcurrent circuit. A current-voltage transforming circuit 21 shown in FIG. 3 is constructed with a transcurrent circuit 22 and a voltage transforming circuit 23.
In the transcurrent circuit 22, a source (S) of a transistor M3 of a P-channel MOSFET is connected to a first power source 24, and a drain (D) thereof is connected to an earth ground (GND) as a second power source through a current source 25.
Further, a source (S) of a transistor M4 of a P-channel MOSFET is connected to the first power source 24, and a drain (D) thereof is connected to the earth ground (GND) as the second power source through a current source 26. In addition, gates (G) of the respective transistors M3, M4 are connected to each other, and the gates (G) is also connected to the drain (D) of the transistor M3.
On the other hand, in the voltage transforming circuit 23, a source (S) of a transistor M5 of a P-channel MOSFET is connected to the first power source 24, and a drain (D) thereof is connected to the earth ground (GND) as the second power source through a current source 27. Further, a gate of the transistor M5 is connected to the drain (D) of the transistor M4. Also, from a drain (D) of the transistor M5, an output voltage V.sub.0 is produced.
In this case, the transistors M3 and M4 have the same gate width W.sub.1 and gate length nL.sub.1, and the transistor M5 has the gate width W.sub.1 and the gate length L.sub.1. Therefore, currents I.sub.3 and I.sub.4 flowing through the current sources 25 and 26 are set to be the same (I.sub.3 =I.sub.4).
In this configuration, when the current I.sub.3 (and I.sub.4) flowing from the current sources 25, 26 into the transistors M3, M4 is flexibly changed a little, a drain voltage of the transistor M4 also varies. When the variation of the drain voltage of the transistor M4 is applied to the gate of the transistor M5, a voltage amplitude V.sub.0 is obtained from the drain (D) of the transistor M5.
In this case, when each voltage at the connection nodes comes close to the voltage of each power source, the voltage amplitude V.sub.0 may decrease. Therefore, in order to prevent the voltage amplitude V.sub.0 from decreasing, a ratio of current values flowing the current paths needs to be maintained.
Namely, so as to maintain the following relationship (2), the gate widths and the gate lengths of the respective transistors M3 to M5 need to be designed. ##EQU2##
FIG. 4A and FIG. 4B show illustrations for explaining a principle of voltage transformation in the current-voltage transforming circuit 21 shown in FIG. 3. FIG. 4A shows a conventional amplifier circuit using a MOSFET M0. In FIG. 4A, a resistor R is connected to a drain of the transistor M0. When an input voltage V.sub.in is applied to a gate of the transistor M0, a drain current I.sub.D is represented by an equation I.sub.D =g.sub.m V.sub.in (g.sub.m is conductance of the transistor M0, and the drain current I.sub.D is obtained as a voltage through the resistor R.
In this case, since an output voltage V.sub.out is determined by an equation V.sub.out =I.sub.D .times.R=g.sub.m .times.V.sub.in .times.R, an amplifying ratio (amplifier gain) is represented by V.sub.out /V.sub.in =g.sub.m .times.R. In the integrated circuit, a value of the resistor R may not be increased enough, because a large forming area is required for the resistor. Therefore, in the circuit shown in FIG. 4A, the amplifying ratio cannot be obtained much.
In the circuit shown in FIG. 4B, a current source 28 constructed with a transistor is provided instead of the resistor R as compared to the circuit shown in FIG. 4A. Using an internal resistor R.sub.ds of the current source 28, in the same way as shown in FIG. 4A, the output voltage V.sub.out is produced. In this case, the amplifying ratio is represented by V.sub.out /V.sub.in =g.sub.m .times.R.sub.ds. As discussed above, the current source 28 is constructed with the transistor. Therefore, the internal resistor R.sub.ds may be formed as a relatively large value, and, thus, the amplifying ratio may be increased.
Returning to FIG. 3, when the current flowing from the current sources 25, 26 is slightly changed, the gate voltage V.sub.GS of the transistor M5 changes, and the drain current flows from the transistor M5. When an internal resistor of the current source 27 is formed as a large value, the amplifying ratio of the voltage transforming circuit 23 may be increased. As a result, a large variation of the output voltage V.sub.0 may be obtained.
However, in the above-discussed transcurrent circuit 11 shown in FIG. 1 and current-voltage transforming circuit 21 shown in FIG. 3, when the gate lengths of the transistors M1 to M5 of the MOSFETs vary, a threshold voltage also changes due to the short channel effect. As a result, the above-discussed equations (1) and (2) may not be defined.
In general, when the layout patterns are formed on the wafer, dispersion of the gate length and the gate width occurs due to imperfect mechanical precision. When a deviation of the gate length due to the dispersion is represented by a symbol ".delta.", the current transform ratio in the transcurrent circuit 11 shown in FIG. 1 is shown in the following equation (3). ##EQU3##
Further, the current transform ratio in the current-voltage transforming circuit 21 shown in FIG. 3 is shown in the following equation (4). ##EQU4##
Therefore, there is a problem in that it is very difficult to achieve a desired current transform ratio due to dispersion of the gate length which occurred in the pattern forming process.
Further, in order to reduce an influence from the dispersion of the gate length which occurs in the pattern forming process, some methods can be used for obtaining a large current transform ratio. For example, a first method is to increase the gate length, and a second method is changing the gate width while maintaining the gate length at the same value. However, the methods of increasing the gate length or the gate width cause the gate region to increase. Therefore, there is a problem in that methods as reducing of the circuit forming area may not be achieved.

Transcurrent circuit and current-voltage transforming circuit using the transcurrent circuit


A distribution manifold includes a main trunk line at a first end of the manifold proximate a boost pump, two branch lines at a downstream end of the main trunk line, a first Y-connector coupling upstream ends of the two branch lines to the downstream end of the main trunk line, two sub-branch lines at a downstream end of each of the two branch lines, and two second Y-connectors coupling upstream ends of the four sub-branch lines to the downstream ends of the two respective branch lines. A sum of cross-sectional areas of downstream ends of the four sub-branch lines is equal to the cross-sectional area of the upstream end of the main trunk line.

Hydraulic fracturing is often used to produce oil and gas in an economic manner from low permeability reservoir rocks. Hydraulic fracturing increases rock permeability by opening channels through which hydrocarbons can flow to recovery wells. During hydraulic fracturing, a fluid carrying proppants in suspension is pumped into the earth under high pressure where it enters a reservoir rock and fractures it, thereby opening and widening channels for oil and gas to flow.
Specialized positive-displacement piston pumps are used to develop the pressures necessary for hydraulic fracturing or "fracking." These pumps typically include fluid ends within the body of which reciprocating plungers place fluids under pressure and valves control fluid flow to and from the plungers. These pumps also include a suction manifold that provides a flow of fluid to the body of the fluid end.
Positive-displacement piston pumps suffer from cavitation when exposed to poor suction conditions on the inlet side of the pump. Chronic cavitation of a pump leads to an extreme reduction in its service life, and can cause extremely early component failure, possibly leading to external leaks and safety concerns with uncontained high-pressure fluid. Hydraulic equipment industry guidelines exist for providing proper suction piping to the inlet of a positive-displacement pump to avoid this issue; however, practical concerns frequently make it difficult for the suction piping to adhere to these ideal guidelines.
A standard practice in hydraulic fracturing is to use a single boost pump (blender) to pressurize a slurry comprised of water, chemicals, and proppant (sand), and then supply that slurry to a group (normally 10-20) of positive displacement reciprocating piston pumps at a nominal pressure, on the order of 100 PSI. These system pumps then operate in parallel with one another to further raise the pressure to the order of thousands of PSI and pump the fluid downhole into the well. Ideally each of the system pumps receives equal suction pressure and flow from the boost pump and therefore operates in a healthy manner and contributes equally to the well stimulation process. In reality, the distribution of slurry from the boost pump to the system pumps is quite challenging due to the physical layout of a well site, including the fact that the pumps are mounted on tractor trailers. The system pumps are general located at variable distances from the boost pump, with some being very close and others being up to several hundred feet away. Achieving a uniform flow distribution between all these pumps is therefore difficult, but is essential to maintaining healthy suction conditions at all pumps, and maintaining a balanced operation across the entire site for good overall well stimulation performance.
Traditional distribution manifolds, which have largely been governed by practical concerns such as ease of construction and transit from one site to another rather than by proper hydraulic pumping design principles, have had a number of shortcomings, including:                being undersized for the desired system pump flow rate, thus limiting the rate at which well stimulation can be performed and risking system pump cavitation;        using extremely tight pipe bend radii and large bend angles, introducing flow restrictions;        featuring sudden changes in pipe diameter, resulting in sudden changes in slurry velocity;        being improperly sized such that velocity is not consistent throughout, leading to some sections where velocity is too high and there is a risk of pump cavitation, and other areas where velocity is too low and there is a risk of proppant fallout and clogging ("sanding off");        providing non-uniform suction pressure conditions to the system pumps; generally providing lower suction pressure to those pumps located at greater distance from the boost pump; and/or        providing non-uniform velocity conditions at ports for system pumps; generally having very high velocities at proximal ports and decreasing velocity at distal ports as the number of pumps drawing from the trunk line decreases.
FIG. 1 illustrates a traditional 10-port manifold design 100. The inlets 110 on the left side of FIG. 1 accept flow from a boost pump 105 and distribute the flow to ten pumps 190 (only five pumps 190 shown in FIG. 1 for clarity) at the ports 120, which are mostly oriented at 90 degrees to the trunk lines 115. Each of the pumps 190 may be, for example, a five-cylinder positive-displacement piston pump such as those described, for example, in co-pending U.S. patent application Ser. No. 16/248,728, filed on Jan. 15, 2019, which is incorporated herein by reference. The trunk lines 115 have a constant cross-section throughout their length. The velocity contours shown illustrate that velocity is very high on the left (proximal end) of the manifold where ten system pumps' worth of fluid is flowing, and velocity decreases to the right (distal end) as fewer and fewer pumps are drawing from the constant cross-section trunk lines 115.
It may be desirable to provide a distribution manifold that provides a more uniform flow and pressure inlet condition at each system pump location along the length of the manifold, thereby making it attainable to instrument the manifold, monitor the now-smaller variations in flow conditions at each system pump port, and adjust the pump RPM or gear to balance flow across the entire system pump fleet. In this regard, it may be desirable to provide a distribution manifold that (i) maintains a constant total cross-section from proximal to distal end, thus achieving constant velocity throughout, (ii) is properly sized to support correct volume flow rates and linear slurry velocities for time-efficient hydraulic fracturing operation without risking proppant fallout or exceeding safe pipe flow rates, (iii) is properly sized to match the suction port size of the system pumps without restricting flow, (iv) eliminates pipe bends of greater than 45-degrees, and/or (v) is optimized for construction on a standard highway tractor trailer such that it can be moved from well site to well site without disassembly. In some embodiments, it may be desirable to provide a distribution manifold that is broken up into 4-pump subsystems such that it can be adapted to larger or smaller well sites requiring different flow rates or total horsepower.

Hydraulic fracturing distribution manifold


An adjustment mechanism for a telescope of a theodolite. The mechanism includes a worm gear that is coupled to a friction gear of the theodolite. The friction gear is coupled to the telescope so that any rotation of the gear will induce a corresponding movement of the scope. The worm gear is coupled to a linear screw and an outer sleeve. The linear screw has a shaft that can push the worm gear and rotate the friction gear to provide a fine movement of the telescope. The linear screw also has a stop that engages an arm of the sleeve. Continued rotation of the linear screw rotates the engaged sleeve and the worm gear to provide a coarse movement of the telescope. The linear screw is connected to a knob which can be rotated by an operator. The operator can induce a coarse movement of the telescope by turning the linear screw so that the stop engages the sleeve. The operator can induce a fine movement of the telescope by rotating the knob in a reverse direction so that the linear screw pushes the worm gear and rotates the friction gear.

1. Field of the Invention
The present invention relates to an adjustment mechanism for moving the telescope of a theodolite.
2. Description of Related Art
Prior art theodolites and total stations typically contain a mechanism to provide coarse and fine movement of the telescope and locking mechanism that locks the telescope in position so that the coarse and fine mechanism can be used to move the telescope. Prior art theodolites and total stations therefore have two separate knobs on both the vertical and horizontal mechanisms that move the telescope in a vertical and horizontal direction. The locking mechanism locks a lever on the axis of the telescope and the coarse and fine mechanism operates against the end of this lever to move the telescope, the reverse direction of the lever, against the movement of the coarse and fine mechanism is typically achieved by a leaf or coil spring. The big problem with this type of mechanism is that the operator is continuously having to unlock and re-lock the locking mechanism in order to return the course and fine mechanism to the center of their run as their lateral movement is limited by the spring that acts against them. This is a great inconvenience to the operator as it takes up valuable time and it makes it almost impossible to track a moving target. It would be desirable to provide a theodolite or total station with a continuous coarse and fine adjusting mechanism for each of the vertical and horizontal alignment of the telescope, and that each mechanism should have only one knob that would move the telescope continuously.