There is proposed an apparatus and method for measuring fluid usage from a container. The apparatus in one form includes a proximity sensor or sensors positioned in, or adjacent, an outlet of said container and configured to monitor the presence or absence of said fluid within or adjacent said outlet, an angle sensor for determining a first angle of said container when said fluid begins to flow through the outlet, and for determining a second angle of said container when said fluid stops flowing through said outlet, and a transmitter for sending data from the proximity sensor/s and angle sensor or processed data therefrom, to a computing device and/or display unit, wherein the data or processed data is used to calculate or indicate a volume of the fluid having passed through the outlet.

It is common nowadays for various metrics of an individual to be measured throughout the day and especially during fitness activities. These parameters are used to measure, compare and track performance of the individual, and may include heart rate, number of steps, sleep duration/quality, intensity of activity and duration. However, one of the metrics that has been difficult to measure has been an individual's hydration. This metric is very important as dehydration during exercise can have severe adverse health effects.
There have been attempts to measure water content of an individual using an infrared light embedded in a wearable, however these have shown only limited success. Various 'smart bottle' have also been released onto the market or are suggested in the published prior art that measure the amount of water consumed and send this data to a wirelessly connected activity tracker, smart watch or smart phone.
One such bottle currently on the market is sold under the H2O-Pal trade mark and comprises a thin module that attaches to the base of a water bottle, which tracks the user's water intake by way of an accelerometer and weight sensor to thereby monitor the water level within the bottle. Notifications are then sent via Bluetooth Smart® to an App on the user's phone. The problem with such devices is that the water bottle must be place down onto a hard surface between drinks for the water usage to be accurately measured, which may not be practical if for instance the person is walking.
Another device is suggested in U.S. Pat. No. 6,212,959 (Perkins) which discloses a liquid-consumption device for estimating an individual's hydration, which includes an impeller located within an outflow channel. The rate of rotation of impeller is proportional to the rate of flow of the fluid passing through the meter and therefore the user's water consumption can be calculated.
Still another device is disclosed in U.S. Patent No. 20160146659 (Saltzgiver et al.) wherein a sensor located within a bottle lid is configured to track changes in a liquid level within a container. The sensor comprising an ultrasonic liquid level sensor configured to indicate the level of the liquid within the container.
The existing 'smart bottle' devices however suffer from various problems, including the expense of the components, power efficiency and in the case of the impeller disclosed in Perkins, may include components are difficult to clean or may become clogged during use.
The phrase "proximity sensor" used throughout the specification should be understood to encompass any type of sensor or switch that is used to detect the presence of a fluid, such as water, at a specific location within a container.
It should be appreciated that any discussion of the prior art throughout the specification is included solely for the purpose of providing a context for the present invention and should in no way be considered as an admission that such prior art was widely known or formed part of the common general knowledge in the field as it existed before the priority date of the application.

Apparatus and method for measuring fluid consumption


A method and system having a probabilistic offload engine for distributed hierarchical object storage devices is disclosed. According to one embodiment, a system comprises a first storage system and a second storage system in communication with the first storage system. The first storage system and the second storage system are key/value based object storage devices that store and serve objects. The first storage system and the second storage system execute a probabilistic algorithm to predict access patterns. The first storage system and the second storage system execute a probabilistic algorithm to predict access patterns and minimize data transfers between the first storage system and the second storage system.

As storage needs increase, solutions have to be found to drive the cost of storage down while maintaining ease of management. Prior solutions move complex storage management into dedicated storage systems. This saves application servers from embedding storage disks directly, and avoids potential inconveniences such as disk failure, data loss, data reconstruction, etc. This also enables economies of scale by managing a shared pool of storage resources more efficiently. Typical technologies include: SAN, Storage Area Networks where storage is centralized into large dedicated proprietary storage cabinets that export their storage capacity in the form of block device volumes, and NAS, Network Attached Storage where medium-sized storage devices export their disks as network file systems. Object stores that do not follow the centralized architecture design can be deployed on large clusters of generic servers, pushing fault tolerance on the software stack rather than onto dedicated storage hardware.
Because SAN technology is block-based, as opposed to file-based, and slices storage capacity into monolithic volumes, solutions derived from this technology cannot perform storage optimization based on the concept of files or objects. These solutions manipulate small, anonymous binary blobs called blocks with no metadata attached to them. Improvements such as thin provisioning, i.e., over-allocation of storage space for each volume to minimize the need for growing existing volumes have evolved. They, however, do not solve the problem at an architectural level and do not solve the underlying issues. For example, most file systems behave poorly with thin provisioning because the file systems assume that they have infinite space so, they do not reuse past blocks and waste space that cannot be reclaimed online, and they require scheduled maintenance down time.

Probabilistic offload engine for distributed hierarchical object storage devices


A silicon nitride sintered body comprising .alpha.-silicon nitride including .alpha.'-sialon and .beta.'-sialon including .beta.-silicon nitride in which the content of the .alpha.-silicon nitride including .alpha.'-sialon in the surface part thereof is less than its content in the inner part thereof. The silicon nitride sintered body is excellent in mechanical strength at ordinary temperature, productivity and cost efficiency.

1. Field of the Invention
The present invention relates to a silicon nitride sintered body having excellent mechanical strengths especially at ordinary temperature and excellent in productivity and cost efficiency.
2. Description of the Prior Art
Various research and development have heretofore been made on the sintering process, sintering aid, restriction of constituent crystal phases and the like for the purpose of enhancing the strength of silicon nitride-based materials. For example, with regard to the sintering process, a sintered body having a bending strength as high as 100 kg mm.sup.2 has been embodied by the hot press sintering process (see Am. Ceram. Soc. Bull., 52 (1973), p.560), and also the hot isostatic press (HIP) process using a glass capsule has been developed. However, these processes cannot be thought to be excellent in productivity and cost efficiency, though excellent strength characteristics of a sintered body can be achieved by them. On the other hand, the gas pressure sintering process can cope with such a problem [see, for example, Mitomo, Funtai to Kogyo 21 (12), 27 (1989)]. However, since in the above process the densification of final sintered product is accompanied by the growth of .beta.-silicon nitride grain, thereby increasing the possibility of causing deterioration in strength due to coarse grain precipitation, and the sintering is carried out usually under a nitrogen gas pressure of 10 atm or higher, the process usually requires large sintering equipment as is the cases with the hot press process and HIP process, thus failing to render itself excellent in characteristics and productivity. Regarding sintering aids, there is disclosed an Si.sub.3 N.sub.4 -Al.sub.2 O.sub.3 -Y.sub.2 O.sub.3 -based silicon nitride sintered body using Y.sub.2 O.sub.3 as the principal sintering aid in Japanese Patent Publication Nos. 49-21091 and 48-38448. As described in the specifications of the above published patents, it is believed that .beta.-silicon nitride grains form a fibrous structure in the sintered body and the structure is dispersed in the matrix, thus enhancing the strength and toughness of the sintered body itself. Specifically, in the aforestated sinter, the fact that .beta.-silicon nitride crystal is hexagonal and anisotropically grows in the direction of C-axis is positively utilized. As indicated in the Japanese Patent Publication No. 48-38448 and J. Ceramic Soc. Japan 94, p96 (1986 ), fibrous .beta.-silicon nitride grains sometimes grow by ten-odd .mu.m or larger in the C-axis direction. The above-mentioned sinter, however, still has a possibility that the grain growth causes the abnormal growth, the occurrence of pores or the deterioration of the strength of the sinter. Moreover, the above sintered body using the sintering aid only cannot be sufficiently densified unless the sintering temperature is raised to 1700.degree. to 1900.degree. C., and sometimes stable sintered products cannot be obtained owing to the sublimation and decomposition of silicon nitride in the case of the nitrogen gas pressure sintering around atmospheric pressure. Accordingly, the above sintered body cannot be said to be sufficiently excellent in the characteristics and productivity. According to any of the above-mentioned sintering processes, the strength of the obtained sintered body is approximately 100 kg/mm.sup.2 at the most expressed in terms of 3-point bending strength, for example, in accordance with JIS R-1601. Thus, considering a variety of applications of silicon nitride-based materials, sufficient characteristics of the materials have not been attained.


Various embodiments of the present disclosure are directed towards a method for opening a source line in a memory device. An erase gate line (EGL) and the source line are formed elongated in parallel. The source line underlies the EGL and is separated from the EGL by a dielectric layer. A first etch is performed to form a first opening through the EGL and stops on the dielectric layer. A second etch is performed to thin the dielectric layer at the first opening, wherein the first and second etches are performed with a common mask in place. A silicide process is performed to form a silicide layer on the source line at the first opening, wherein the silicide process comprises a third etch with a second mask in place and extends the first opening through the dielectric layer. A via is formed extending through the EGL to the silicide layer.

Many modern electronic devices include flash memory. Flash memory is an electronic non-volatile computer storage medium that can be electrically erased and reprogrammed. To store information, flash memory includes an addressable array of memory cells, typically made from floating gate transistors. Common types of flash memory cells include stacked-gate flash memory cells and split-gate flash memory cells (e.g., a third generation SUPERFLASH (ESF3) memory cell). Split-gate flash memory cells have lower power consumption, higher injection efficiency, less susceptibility to short channel effects, and over erase immunity compared to stacked-gate flash memory cells.

Etch method for opening a source line in flash memory

Taiwan Semiconductor Manufacturing Company, Ltd.


High density heatsinks for microcircuit packages are formed by first mold-pressing a composite powder of free-flowing spray-dried particles of an inexpensive high thermal conductivity material having a high coefficient of thermal expansion (CTE) such as copper and at least one other low CTE material such as tungsten, the proportions of which are adjusted to match the CTE of the microcircuit material. The pressed compacts are sintered in order to achieve an homogeneous distribution of the melting copper throughout the structure. A multilevel embodiment of the heatsink comprises two bonded layers of metals or composites having their coefficients of thermal expansion adjusted to match those of the semiconductor material and of any supporting structures respectively, wherein the second layer in contact with the supporting structure has a high CTE and the other has a lower CTE. Another embodiment provides for bonding a composite heatsink to a high thermal conductivity pedestal which mounts the microcircuit device, using sintering to shrink an aperture engaged by the pedestal.

The fabrication of electronic microcircuits requires the use of substrates, heatsinks, electrodes, leads, connectors, packaging structures and other components capable of dissipating the heat generated by the active parts of the microcircuit or by the soldering, brazing or glass-sealing process. Moreover, those components that are in direct contact with the active microcircuit sections must have a coefficient of thermal expansion ("CTE") compatible with gallium arsenide, silicon, germanium or any material used in the fabrication of the microcircuit.
Materials such as copper, silver, gold and aluminum which exhibit high coefficient of thermal conductivity tends also to have CTEs much higher than materials such as gallium arsenide alumina or polysilicon which are used in the implementation microcircuit elements or their enclosures.
As disclosed in U.S. Pat. No. 4,680,618 Kuroda et al., it has been found convenient to use composites of copper and other denser metals such as tungsten or molybdenum in the fabrication of heatsinks, substrates and other heat-dissipating elements of microcircuits. The proportions of the metals in the composite are designed to match the CTE of the material used in the fabrication of the active circuit component.
The CTE of a metal is defined as the ratio of the change in length per degree Celsius to the length. It is usually given as an average value over a range of temperatures. Metal used in electrical conductors such as aluminum, copper, silver and gold that have a low electrical resistivity also exhibit high coefficients of thermal conductivity. The coefficient K of thermal conductivity of a material is defined as the time rate of heat transfer through unit thickness, across unit area, for a unit difference in temperature or K=WL/A T where W=watts, L=thickness in meters, a=area in square meters, and T=temperature difference in .degree.K. or .degree.C. For copper, K is equal to 388. For silver, K is equal to 419. However, these metals exhibit an average CTE in excess of 15.times.10.sup.-6 /.degree.C. By contrast, material such as gallium arsenide and silicon, that are commonly used in the manufacture of microcircuit chips have an average CTE of less than 7.times.10.sup.-6 /.degree.C. Thus, while material of high electrical and thermal conductivity are favored in the fabrication of heat-dissipating electric elements, they must be blended with conductive material exhibiting a much lower average CTE in order to create a composite whose thermal expansion characteristic comes as close as practically possible to that of gallium arsenide, silicon and other micro-chip materials. Tungsten and molybdenum with average CTE of 4.6.times.10.sup.-6 /.degree.C. and 6.times.10.sup.-6 /.degree.C. and coefficient of thermal conductivity of 160 and 146 respectively are favored.
However, while copper, aluminum, and silver have specific gravities of less than 9, and melting point of less than 1,100.degree. C., tungsten and molybdenum have specific gravities of 19.3 and 10.2, and melting points of 3,370.degree. C. and 2,630.degree. C. respectively.
Due to the large differences in the specific gravities and melting-points, and lack of mutual solubility of metals such as copper and tungsten, for example, it is difficult to form composites of those two metals that exhibit a reliable degree of homogeneity using conventional melting processes.
As disclosed in U.S. Pat. No. 5,086,333 Osada et al., it has been found more practical to press and sinter a powder of the most dense materials, e.g., tungsten, to form a porous compact, then to infiltrate the compact with molten copper or another lighter material. A slab of the resulting material can then be cut and machined to form heatsinks, connectors, substrates and other heat-dissipating elements.
The heat-dissipating base upon which micro-chips are mounted must also be attached to packaging or frame member usually made of ceramic or other material having a different CTE than the semiconductor material of the micro-chip and of the heat-dissipating base. Thermal stress between the heat-dissipating base and the frame member may cause cracks or camber after joining operation in the latter stage. The problem has been addressed in the prior art by using a intermediate heat-dissipating member whose composition and CTE continuously vary from one contact to the other as disclosed in U.S. Pat. No. 3,097,329 Siemens.
Another approach disclosed in U.S. Pat. No. 4,427,993 Fichot et al. consists of embedding a lattice of CTE-modifying material into one of the contact surfaces of the heat-dissipating element.
Both of these approaches are, complex and onerous and do not allow a precise control of the CTEs at one or both interfacing areas of the heat-dissipating member.
The costs of metals such as tungsten and molybdenum are relatively high compared to the costs of copper, aluminum and other more abundant metals. Heat-dissipating components made of composites in which a costly metal such as tungsten is used for CTE-matching purpose tend to be expensive. As the power ratings of micro-electronic modules increase, bigger heat-dissipating substrates are required. The cost associated with the substrates being dictated by the cost of their base metals remains inflexibly high while the costs of the microcircuit can be controlled and even reduced through the use of new technological improvements. The problem of substrate-related costs is particularly acute in microwave power devices where large and elaborate heat-sinks must be used. In many cases, the costs of the heat-dissipating component represent a large percentage of the total device. Accordingly, there is a need for a more economical way to construct heat-dissipating substrates for high-power micro-electric modules.
The instant invention results from an attempt to devise a simpler, more practical and more economical process to manufacture such heat-dissipating components using powder and other metallurgy techniques. The invention is based in part on the techniques and processes disclosed in the parent application, Ser. No. 08/064,255 which issued as U.S. Pat. No. 5,413,751 dated May 9, 1995, which application and patent are hereby incorporated in this Specification by reference.

Heat-dissipating package for microcircuit devices and process for manufacture


A multi-chip semiconductor apparatus includes a plurality of semiconductor chips stacked and packaged therein, wherein each of the semiconductor chips includes: a through-silicon via (TSV) formed through the semiconductor chip; a probe pad exposed to an outside of the semiconductor chip so as to enable a probing test; a bump pad exposed to the outside of the semiconductor chip and electrically connected to the TSV; and a conductive layer electrically connecting the probe pad and the bump pad inside the semiconductor chip.

1. Technical Field
Various embodiments presented herein relate to a semiconductor apparatuses, and more particularly, to a multi-chip semiconductor apparatuses including a plurality of semiconductor chips stacked through through-silicon vias (TSVs).
2. Related Art
Packaging technology for semiconductor apparatuses has continuously developed to satisfy demands for miniaturization and reliability of mountings. For example, the demand for miniaturization has accelerated the technology development for packages which are close to chip size. The demand for more reliable mountings has driven the importance and development of packaging technologies capable of improving the efficiency of mounting operations and the mechanical/electrical reliability after mounting.
Furthermore, as high performance electric and electronic products are required with miniaturization, various technologies for providing a high-capacity semiconductor module have been researched and developed. As a method for providing a high-capacity semiconductor module, high integration for memory chips may be used. This high integration may be realized by integrating a larger number of cells into a limited space of a semiconductor chip. However, such high integration for memory chips requires a high-level technology and a large amount of development time. For example, a fine critical dimension (CD) may be required. Therefore, improved stack technology may provide benefits in a high integration environment.


The method of lifting a generator rotor shaft (12) off its bearing (10) to enable breakaway during start-up and for maintenance purposes includes providing a hydraulic cylinder (22) with a pair of rollers (28) mounted on the cylinder piston (32) engageable with the shaft (12). At start-up, the cylinder is actuated to elevate the shaft a maximum distance of about 0.005 inches to enable a film of lubricating oil to flow between the shaft journal and the bearing pads. For maintenance purposes, and after removal of the upper bearings, the shaft can be elevated by actuation of the jack a distance sufficient to enable removal of the lower bearings from the pedestal.

When a rotor shaft mounted in bearings has not been rotated for a period of time, the oil film between the rotor shaft journal and the lower bearing surfaces becomes extremely thin or nonexistent. Metal-to-metal contact between the shaft journal and the lower bearing surfaces sometimes occurs in view of the weight of the rotor shaft, e.g., on the order of 20 or more tons, on the lower bearing surfaces. The reduced oil film or metal-to-metal contact between the rotor shaft journal and the lower bearing surfaces results in an inability to rotate the rotor shaft at start-up in the absence of a very high breakaway torque applied to the shaft. Apart from the undesirability of a high breakaway torque, it causes problems in routine maintenance of the shaft and bearings. For example, the lower bearings cannot be removed because of the weight of the shaft resting on those bearings. Additionally, even if the shaft is jacked up, most jacking-type devices do not permit the shaft to rotate for maintenance purposes while elevated off the lower bearing surfaces.
These problems, to some extent, have previously been recognized. Systems exist to facilitate initial rotation and start-up of a generator rotor shaft. For example, hydrostatic systems employing high-pressure oil feeding through the lower bearing surfaces have been used to essentially raise the shaft journal from the bearing sufficiently to permit the formation of an oil film between those surfaces, whereby the rotor shaft can be readily rotated with minimum starting torque. Such hydrostatic systems, however, involve complicated bearing structure, including the necessity to route high-pressure oil through passages and orifices in the bearings and bearing surfaces. Furthermore, such high-pressure oil systems cannot be used in routine maintenance, particularly, when the upper bearing surfaces have been removed. Thus, this added expense and complexity does not cure both start-up and maintenance problems. Other types of devices for lifting the rotor from the bearing such as jacks or wooden cribbing have also been used. Use of these, however, is oftentimes awkward and dangerous.

Method for lifting a generator rotor shaft to facilitate shaft breakaway and maintenance


A cell evaluation system includes physical measurement unit, a database, and evaluation unit. The evaluation unit refers to a relevance stored in the database, searches reference measurement information based on measurement information of a cell newly measured via the physical measurement unit, and evaluates the cell with biological measurement information associated with the searched reference measurement information.

The smallest unit that constitutes an organism is a cell. Conventionally, various clarifications on functions, structures, forms, and the like of the organism have been carried out only for cell groups, but not carried out for the unit of individual cell constituting them.
However, recently, it has been found that gene expression is different for each cell even in a cell type having similar phenotype in a cancer tissue and the like. Therefore, instead of carrying out the various clarifications on a cell group basis, it is necessary to perform analyses on an individual cell basis.
As a cell measurement technique for such analysis with one cell (single cell), there has been proposed a flow cytometry method. The flow cytometry method is a technique where individual cells are dispersed in a fluid, and the fluid is finely flown down to be optically analyzed, and an apparatus using this technique is referred to as a flow cytometer. In the flow cytometry method, an observation target can be evaluated by irradiating microparticles such as cells as the observation targets with an excitation light while flowing down the microparticles through a flow passage at a high speed to obtain a total amount of a fluorescence intensity and/or scattered light emitted from the individual cells. The use of the flow cytometry method allows the analysis of the single cell with a very high throughput. Patent Document 1 discloses a flow cytometer and a flow cytometry method using the flow cytometer.
As a method for observing the phenotype of the individual cell in more detail, there has been known a fluorescence microscope and an imaging cytometer. These observation methods can obtain not only one-dimensional information such as the total amount of the fluorescence intensity and/or the scattered light emitted from the observation target, but also two-dimensional or three-dimensional morphological information. Meanwhile, different from the flow cytometer, because the observation target does not move, it is difficult to perform the single cell analysis in large scale with high throughput in these observation methods. In this respect, there has been known imaging flow cytometers that can take an image of the cell morphology information at high speed with a throughput equivalent to that of conventional flow cytometers (for example, see Patent Document 2), and the cell phenotype can be evaluated with two-dimensional or three-dimensional space information including fluorescent cell images. This ensures dramatical increase in the amount of information available for cell analysis while keeping the throughput of the existing flow cytometry method, and thus ensuring the improved quality and quantity in the cell phenotype analysis.
Furthermore, for effective use of the enormous volume of the cell morphology information generated by the imaging flow cytometer, there has been proposed a method where machine learning is used for the cell morphology information to evaluate and classify the cell (for example, see Patent Document 3). Specifically, there has been a method using, for example, a supervised machine learning where correct-information (teacher data) is provided in advance to configure a classifier and then the provided cell information is evaluated and classified, and an unsupervised machine learning where the provided cell information is evaluated and classified without the correct-information provided in advance.    Patent Document 1: Japanese Patent No. 5534214    Patent Document 2: U.S. Pat. No. 6,249,341    Patent Document 3: Japanese Patent Application No. 2015-212356 (Published as WO 2017/073737)

System and method for cell evaluation, and cell evaluation program


The present disclosure pertains to novel cell cultivation and cell and/or cell-derived product production processes that have advantages over currently existing fermentation strategies. The processes and methods according to the present disclosure may be used for an efficient supply of highly viable and metabolically active eukaryotic cells for transient production platforms, as an alternative production process with advantages over currently applied processes (batch, fed-batch or perfusion strategies) and for generating metabolically highly active biomass for subsequent use for transient expression systems or infection by a virus or pseudovirus or in cell-free systems.

Manufacturing of biopharmaceuticals is subject to many changes, such as rising volume demands and more stringent safety requirements. In addition, product quality, product yields, production costs and facility utilization are important aspects for the biopharmaceutical industry. Thus there is continued interest in further optimizing and refining conventional manufacturing platforms and to develop novel ones that are capable of resolving current bottlenecks as well as to enable novel and innovative production processes.
The use of fermenters in the biotechnology industry as a rule currently involves batch, fed batch or continuous bioreactor processes for preparation of fermentation solutions, production of biomass and manufacture of fermentation products. The mode of feeding the bioreactors determines whether a bioreactor or fermenter is classified as batch, fed batch or continuous bioreactor.
If the bioreactor is only filled once without further feeding (i.e. addition of media containing nutrients) the bioreactor is operating in batch mode. The bioreactor will be allowed to run till completion. At the end of the run the fermentation is terminated and the products are harvested, before a new fermentation is initiated again.
These batch procedures customarily include inoculation of a nutrient medium with the desired culture, cultivation for a specific time under precisely defined conditions, and harvesting of the microorganisms and/or recovery of the desired products of metabolism.
In Detail Batch Fermentation:
A batch fermentation is once filled with medium and inoculated. After inoculation the reactor is a closed system except for a few additives like oxygen and base/acid for controlling the pH. This means that once the fermentation is started no additional media or nutrients will be fed into the reactor. So the reactor culture volume is constant over the entire process (except for volume losses due to evaporation). Several important cell culture parameters are changing over the process, e.g. cell density, viability, dissolved oxygen, nutrient and product concentration. The cell culture undergoes a lag, exponential and stationary growth phase. When harvest conditions are reached the process is finished and the total fermentation broth will be harvested. To produce more products, the process is repeated or scaled to larger vessels.
In Detail Repeated Batch Fermentation:
A repeated batch fermentation is operating in normal batch mode after inoculation. The culture parameters like cell density, dissolved oxygen, nutrient and product concentration are changing over the entire process. The bioreactor will be allowed to run till completion. At the end of the run the fermentation broth is harvested under sterile conditions but a fixed volume of fermentations broth remains in the bioreactor and served as the new inoculum. The reactor is filled with fresh medium again and a new batch fermentation cycle starts. Cells in that operation mode undergo a new adaption, exponential and stationary growth phase each cycle. The repeated batch fermentation increases the overall process efficacy of batch and fed-batch processes by saving the time for preparing the fermenter and inoculum. While ideally the repeated batch is essentially identical to the batch cultivation, memory effects and carry-over from the previous cultivation are of concern, especially for production of pharmaceutical proteins.
However, a number of disadvantages are associated with these several batch processes. In batch fermentations growth of microorganisms and living cells generally occurs under varying and sometimes unfavorable conditions. At the beginning of the fermentation the cells require time (lag-phase) to adapt to the medium. The viable cell density (inoculum viable cell count) is at its lowest level in the presence of the highest substrate concentration, which can even lead to substrate inhibition or to suppression of growth due to the high osmolarity of the medium.
In a continuous fermentation sterile nutrient solution is fed to bioreactor continually with a specific rate and an equivalent volume of fermentation broth is simultaneously removed from the bioreactor to keep the culture volume in the bioreactor essentially constant over the entire process.
The growth rates of the organism will be controlled by the rate the medium is pumped in depending on the maximal growth rate of the culture. The fresh medium rate (so called dilution rate) needs to be lower than 90% of the maximal specific growth rate of an organism. The relative low doubling times of mammalian and plant cells (approximately 1 per day) is resulting in low dilution rates and therefore the washed out fermentation broth have to be collected over longer time periods. This so called a hold step of the harvest has several disadvantages. First, the harvested cells are kept under unfavorable conditions, as the harvest container does not comprise the same level of complexity as the fermenter. Typically a number of parameters are not controlled anymore. The change in conditions leads to lower cell viability and cell rupture causes release intracellular contaminants such as host cell proteins and host cell DNA. Product quality can be compromised through several mechanisms including proteolytic degradation or altered post-translational modifications. The definition of a batch in regulatory terms is also more difficult. Batch-to-batch consistency is a critical issue because minor changes in the growth rate, which can e.g. be caused by subtle differences in media batches, can cause large changes in the process. For biopharmaceutical products such processes then have to be terminated and the products have to be rejected.
In Detail Continuous Fermentation (Chemostat/Turbidostat)
Both operation modes are continuous processes with a fixed reactor volume that aim for a constant cell density. In both processes fresh medium is continuously fed to the reactor while simultaneously the same volume of fermentation broth is harvested. The culture volume is kept constant over the entire process, thus the amount of fresh medium that is added has to be equal to the amount of culture broth that is removed. Fresh medium input and fermentation broth output therefore depend on each other.
In the chemostat process, fixed flow rates for adding the fresh medium (=feed rate) and removing the culture broth (=harvest rate) are used. The flow rates are identical and are called the dilution rate, i.e. the culture volume in the fermenter is maintained constant. Once the cell culture has adapted to the external conditions the process is in a stable steady state and the growth rate matches the feed rate. If the system is disturbed such that the growth rate is affected, which can for example be the case when a new batch of medium is used, or when metabolic products accumulate over time, the system can become unstable. In particular if the growth rate is reduced, the cells are washed out and the cell density decreases steadily. The increase of the cell number in the culture also depends on the volume. As a result, fermentation broth cannot be harvested at will without disturbing the process. Moreover, the cell density of a stable chemostat process is a result of the external conditions (nutrients, temperature, aeration . . . ) and cannot be defined otherwise by the operator. In the turbidostat process the dilution rate is controlled by the turbidity such that the cell density and culture volume in the fermenter remains constant over time. Culture broth is continuously removed from the fermenter and is stored in a collection vessel. Fermentations operated in the chemostat/turbidostat mode provide culture broth and products contained therein by continuously harvesting small fractions of the culture grown in the vessel. The small fractions have to be collected and stored over extended periods in a container. Especially for biopharmaceuticals such a hold-step is not desirable because it is a source of variation and can negatively impact the product quality. For example, cell-lysis may occur during the hold step, proteases may degrade the product or post-translational modifications may be affected which again increases the variation and has impacts on the product quality. Hold-steps are even more undesirable in cases where the cells or compositions derived from these cells comprise the product. The hold step reduces cell viability, metabolic activity and reproducibility.
Continuous fermentations are advantageous because they have a significantly higher space-time yield as compared to batch and fed-batch processes. Thus, they require a lower facility size for achieving the desired production capacity and this also means that investments for building the production facility are lower.
Despite the ideal characteristics of the continuous bioreactor, the process itself is sensitive and subjected to influence from various factors such as risks of contaminations, cell or biomass washouts, and changes in the biotic phase of the bioreactor.
Fed Batch is the intermediary model of bioreactor operation. A proper feed rate, with the right component constitution is required during the process. Fed-batch offers many advantages over batch and continuous cultures. From the concept of its implementation it can be easily concluded that under controllable conditions and with the required knowledge of the microorganism involved in the fermentation, the feed of the required components for growth and/or other substrates required for the production of the product can never be depleted and the nutritional environment can be maintained approximately constant or at the required level during the course of the fermentation. The production of by-products that are generally related to the presence of high concentrations of substrate can also be avoided by limiting its quantity to the amounts that are required solely for the production of the biochemical. When high concentrations of substrate are present, the cells get "overloaded", this is, the oxidative capacity of the cells is exceeded, and due to the Crabtree effect, products other than the one of interest are produced, reducing the efficacy of the carbon flux. Moreover, these by-products prove to even "contaminate" the product of interest, such as ethanol production in baker's yeast production, and to impair the cell growth reducing the fermentation time and its related productivity (Chmiel 2006).
In Detail Fed Batch Fermentation:
A fed-batch fermentation starts with a classical batch phase. When certain conditions are reached the feed is started, i.e. additional nutrients are provided. In this operation mode the reactor culture volume is constant in the batch phase and in the feeding phase the volume increases. In this mode also several culture parameters are changing and the cells undergo classical growth phases. Like in the batch fermentation the total reactor volume will be harvested at the end of the process.
In batch and fed-batch fermentation the cell viability is declining in the later stages and the harvest time point has to be selected carefully to ensure high and consistent product quality. Cells can experience high stress due to metabolic burden. Dying and rupturing cells release intracellular matter, e.g. host cell proteins and DNA as well as product related impurities into the media, which can also be of concern.
However, almost all therapeutic antibodies are currently produced using fed-batch fermentation strategies or perfusion-strategies. Certain regulatory aspects such as batch definition and time requirements for process development (technical runs, repeatability) and general concerns (see hold step, product stability and quality) as well as a typical reluctance within the pharmaceutical industry for new or different technologies have all contributed to the huge dominance of fed-batch methods. This is even though there are several issues that are problematic, as e.g. product quality and post-translational modifications, in particular for antibody products where N-glycosylation is a critical property. In many cases fed-batch cultures are incubated for long times to maximize yields, but cell viability significantly decreases towards the end of the cultivation period, liberating intracellular product, host cell proteins and host cell DNA. The down-side of this is or can be lower product quality or higher product heterogeneity (e.g. glycoforms), eventually leading to a higher failure rate (out-of specification batches) or lower product performance (i.e. clinical efficacy).
Furthermore, low running-to-set-up-times ratio for batch and fed-batch fermentations is currently compensated by investments of men-power and infrastructure. Switching to continuous modes can sometimes circumvent this but this is not always possible and not always desirable. Problems related to product homogeneity occurring during stationary phase in batch/fed-batch/repeated batch fermentation can be addressed or avoided by harvesting/terminating the process before the stationary phase is reached. However, significantly lower product yields then have to be accepted. Differences in product quality are a frequent cause for batch rejection, i.e. the whole material has to be thrown away and the invested costs are not recovered.
Recently production technologies using transient gene expression in eukaryotic cells have gained considerable interest (Derouazi, Girard et al. 2004 Biotechnol Bioeng; Geisse, Jordan et al. 2005 Methods Mol Biol; Hacker, Derow et al. 2005 J Biotechnol). This is for several reasons, including higher yields as compared to transgenic systems (e.g. transgenic plants), short production cycles (days vs. month or even years), fast response times, particularly in emergency situations (pandemics, personalized medicines) and faster product and clinical development. Transient production systems require large amounts of wild type (i.e. non-transformed) cells for transfection/transformation because the cells are not incubated over long time periods and cell growth and cell division is typically low or does not occur at all. It is obvious that the wild type cells used as hosts for transient gene expression critically affect the yield and quality of the resulting products. Moreover, a high reproducibility is very important for products that are destined for clinical trials.
For transient production technologies the reproducible production of highly viable cell material is one of the most crucial bottlenecks.
Cell-free systems, including in-vitro transcription and in-vitro translation have also gained significant interest, in particular for High-Throughput screening and synthetic biology applications. Particular advantages are (amongst others) that cell-free systems can be modified in ways not amenable to whole cells, that nucleic acids can be directly added without the need for technologies to deliver them through cell walls and cell membranes into the cell, experiments can be standardized and that there are multiple ways for measuring readouts. Cell-free systems are particularly amenable to down-scaling and automation. As for transient expression systems, reproducible production technologies for highly active components required for cell-free systems currently represent a significant bottleneck.
Therefore, it was the object of the present disclosure to overcome the disadvantages of the current fermentation technologies for providing improved cell biomass or cell-derived products.

FRAUNHOFER-GESELLSCHAFT ZUR FOERDERUNG DER ANGEWANDTEN FORSCHUNG E.V.


A device receives content data associated with a collection of content that is available to a user. The device determines, by processing the content data using a first data model that has been trained using machine learning, measures of likelihoods that the user will be receptive to each respective content of the collection of content. The device determines a duration during which the user is predicted to engage in a content watching session by using a second data model to process at least a portion of the content data. The device determines measures of utility that correspond to the collection of content and that measure utility that each respective content is predicted to have to the user during the content watching session. The device determines content recommendations for the user based on the measures of utility and causes at least one content recommendation to be displayed.

Linear content may refer to content that is delivered at a scheduled time period. For example, an individual may turn on a TV (e.g., using a remote control) and may tune in to a channel that is broadcasting content during a scheduled time period. As another example, an individual may have a subscription to a streaming service that allows the individual to watch streamed content that is broadcast during a scheduled time period. Video on-demand (VOD) content (sometimes referred to as non-linear content) may refer to content that is available to users at any time period. For example, an individual may have a subscription to a streaming service and may stream recorded content at any time period via one or more laptop computers, mobile devices, and/or the like.

Systems and methods for recommending linear content


Exercise dumbbells have pairs of weights disposed at opposite ends of a handle. Selector rods are selectively movable into engagement with various combinations of the weights.

Exercise dumbbells are well known in the art and prevalent in the exercise equipment industry. Generally speaking, each dumbbell includes a handle and a desired number of weights or plates which are typically secured to opposite ends of the handle. The dumbbell is lifted up subject to gravitational force acting on the mass of the handle and any attached weights.
Some prior art dumbbells are made as fixed weights, and some people seem to prefer fixed weight dumbbells, perhaps because they are simple to use and solid in construction. However, a disadvantage of fixed weight dumbbells is that numerous such dumbbells are required to provide a range of weight resistance.
Other prior art dumbbells include handles and weight plates that the user is able to add to and/or remove from the handles. These variable weight dumbbells provide an economy of scale because only a few weights may be combined in a variety of ways to provide a range of weight resistance. On the other hand, these variable weight dumbbells require time to change between levels of weight resistance (particularly since a change is typically made to each end of two separate handles), and the loose weight plates present a storage problem, as well.
Still other prior art, adjustable weight dumbbells (and barbells) do not require the user to handle the weight plates during changeovers, and they maintain the weight plates in orderly fashion when not in use. Examples of these more sophisticated, "self-adjusting" free weight assemblies are disclosed in U.S. Pat. No. 4,284,463 to Shields (discloses a dumbbell assembly having opposite side weights which are maintained in alignment on a base and selectively connected to a handle by means of cam driven pins on the weights); U.S. Pat. No. 4,529,198 to Hettick, Jr. (discloses a barbell assembly having opposite side weights which are maintained in alignment on respective storage members and selectively connected to a handle by means of axially movable springs); U.S. Pat. No. 4,822,034 to Shields (discloses both barbell and dumbbell assemblies having opposite side weights which are maintained in alignment on a shelf and selectively connected to a handle by means of latches on the weights); U.S. Pat. No. 5,769,762 to Towley, III et al. (discloses various weight assemblies having a plurality of interconnected opposite side weights which are stored in nested relationship to one another and selectively connected to a handle by various means); and U.S. Pat. No. 5,839,997 to Roth et al. (discloses a dumbbell assembly having opposite side weights which are maintained in alignment on a base and selectively connected to a handle by means of eccentric cams on a rotating selector rod.

This patent is subject to a terminal disclaimer.

Exercise weight selection methods and apparatus


An apparatus for controlling a refrigerant level comprises a first detecting unit installed at a lower side of the inside of a refrigerant tank, for detecting whether a refrigerant stored at a lower side of the inside of the refrigerant is a liquefied refrigerant or a gaseous refrigerant, a second detecting unit installed at an upper side of the inside of the refrigerant tank, for detecting whether a refrigerant stored at an upper side of the inside of the refrigerant tank is a liquefied refrigerant and a gaseous refrigerant, and a control unit controlling intake and discharge of the liquefied refrigerant according to a value measured by the first detecting unit and the second detecting unit.

1. Field of the Invention
The present invention relates to an apparatus for controlling a refrigerant level, and particularly, to an apparatus for controlling a refrigerant level which can control a level of a refrigerant stored in a refrigerant tank.
2. Description of the Conventional Art
FIG. 1 is a longitudinal sectional view that illustrates a refrigerant tank provided with a conventional apparatus for controlling a refrigerant level.
As shown in FIG. 1, the refrigerant tank 10 provided with a conventional apparatus for controlling a refrigerant level has a space portion 12 for storing a refrigerant in a main body 11.
An intake pipe 13 through which a liquefied refrigerant 12a is received is formed at an upper portion of the main body 11 of the refrigerant tank 10, and a discharge pipe 14 through which the liquefied refrigerant 12a is discharged is formed at a lower portion of the main body 11 of the refrigerant tank 10.
An intake valve 13a for the refrigerant intake into the main body 11 of the refrigerant tank 10 is installed at the intake pipe 13, and a discharge valve 14a for discharging a refrigerant is installed at the discharge pipe 14.
An insertion hole 11a is formed at an upper end of the main body 11 of the refrigerant tank 10, and a sealing member 11b for sealing the insertion hole 11a is coupled to the insertion hole 11a.
An apparatus for controlling a refrigerant level using a specific gravity difference between a float and a refrigerant is provided at the space portion 12 of the main body 11 of the refrigerant tank 10.
The conventional apparatus for controlling a refrigerant level includes a guide 15 installed long in a vertical direction in the main body 11 of the refrigerant tank, floats 16 and 17 respectively formed at an upper portion and a lower portion of the guide 15, and stoppers 18 and 19 respectively installed at upper and lower sides of the floats 16 and 17.
Here, the specific gravity of the float 16 and 17 is smaller than that of the liquefied refrigerant 12a, and is greater than that of the gaseous refrigerant 12b. In general, if apparatus for controlling a refrigerant level is a low pressure type in which the inside of the main body 11 of the refrigerant tank 10 is in a low pressure state, the floats 16 and 17 are formed of rubber in a spherical body, and if the device is a high pressure type in which the inside of the main body 11 of the refrigerant tank 10 is in a high pressure state, the floats 16 and 17 are formed of metal in a spherical shape. A gas is injected in the floats 16 and 17.
The stoppers 18 and 19 limit a range within which the corresponding floats 16 and 17 ascend and descend.
However, technically, it is difficult to seal, with the sealing member, the insertion groove formed at an upper end of the main body of the refrigerant tank provided with the conventional apparatus for controlling a refrigerant level. In this case, the refrigerant leaks from a gap of the sealed portion.
Also, if the height of the main body of the refrigerant tank gets higher, the height of the guide should get higher as much. Therefore, the entire structure becomes complicated, the manufacturing cost increases, and it is difficult to install the float at the guide.
Also, in case of the high pressure type float, the float itself is deformed by the pressure of the gas injected therein.

Apparatus for controlling refrigerant level


A system and method of scheduling communication in a wireless communication network are provided. An access node can determine a scheduling scheme based on an indication of data addressed to wireless devices. The scheduling scheme can comprise a first subframe and a second subframe comprising a first and second resource block. The scheduling scheme can be communicated. Data addressed to the wireless devices in communication with a first access node can be transmitted during the first subframe and the first resource block of the second subframe. A second access node can be instructed to assign data addressed to wireless devices that meet a signal condition threshold to be transmitted during the second resource block of the second subframe and to assign data addressed to wireless devices that do not meet the signal condition threshold to be transmitted during the first subframe and the first resource block of the second subframe.

Wireless communication can be used as a means of accessing a communication network. Wireless communication has certain advantages over wired communications. For example, implementing a wireless interface can eliminate a need for a wired infrastructure thereby reducing the cost of building and maintaining network infrastructure. In addition, a wireless network can support added mobility by allowing a wireless device to access the network from various locations or addresses. A wireless interface can comprise at least one transceiver in active communication with another transceiver that is connected to the network.
Various types of network configurations can be used to communicate data over the wireless network. For example, a heterogeneous network can be configured to include various types of access nodes such as a macro access node, a micro access node, a pico access node, a femto access node, etc. In a heterogeneous network, a wireless device can be served by an access node having the lowest signal path loss rather than by an access node having the strongest signal strength as in traditional network configurations.
In a heterogeneous network, interference can occur at the cell edge of the short range, low power access nodes due to the macro access node. This interference can result in undesirable reduction in coverage and throughput to the wireless devices in communication with the short range access node. A scheduling scheme comprising an almost blank subframe (ABS) can be used to create an opportunity for the wireless devices within the cell edge region of a short range access node to receive downlink information without interference from the macro access node. However, the capacity of a macro access node can be reduced due to the increase in ABSs in a scheduling scheme.
Overview
A system and method of scheduling communication in a wireless communication network are provided. A first access node can determine a scheduling scheme based on a first indication of data addressed to wireless devices in communication with the first access node and a second indication of data addressed to wireless devices in communication with a second access node. The scheduling scheme can comprise a first subframe and a second subframe where the second subframe comprises a first resource block and a second resource block. The scheduling scheme can be communicated from the first access node to the second access node. Data addressed to the wireless devices in communication with the first access node can be transmitted during the first subframe and the first resource block of the second subframe. The first access node can refrain from transmitting data addressed to the wireless devices in communication with the first access node during the second resource block of the second subframe. The second access node can be instructed to assign data addressed to wireless devices in communication with the second access node that meet a signal condition threshold to be transmitted during the second resource block of the second subframe of the scheduling scheme and to assign data addressed to wireless devices in communication with the second access node that do not meet the signal condition threshold to be transmitted during the first subframe and the first resource block of the second subframe of the scheduling scheme.

Method of scheduling communication in a wireless communication network


An optical waveguide is constructed so as to comprise a non-solid core surrounded by a solid-state material. The non-solid core has an index of refraction which is lower than the index of refraction of the surrounding solid state material, and light can be transmitted with a low loss through the non-solid core. The non-solid core can extend through at least one of multiple layers of the solid state material, wherein the non-solid core is elevated on a substrate material above at least one topmost layer of the multiple solid state layers lateral to the non-solid core. In an exemplary application, the non-solid core comprises a sample material whose light transmission, absorption, and/or interference characteristics are to be measured.

The present invention improves upon the loss characteristics of an optical waveguide and related measurement system of the kind described in U.S. patent application Ser. No. 10/868,475, filed Jun. 15, 2004, "Apparatus For Optical Measurements On Low-Index Non-Solid Materials Based On Arrow Waveguides", which is hereby incorporated by reference in its entirety. This application was published on Dec. 16, 2004, with Publication Number US20040252957A1.

The Regents of the University of California


The invention relates to sun-protection agents containing (a) water soluble xcex2-(1,3) glucans that are substantially devoid of xcex2-(1,6) links, and (b) UV sun-protection factors.

The invention relates to the field of sun cosmetics and concerns to novel preparations with a content of specific glucans and UV light protection factors as well as the use of the glucans for improvement of the photosensitivity of the light protection factors.
The cosmetic sun protection products protect the human skin not only against the direct results of UV-A and UV-B radiation, i.e. against sunburn, but also against the indirect results in the form of skin aging and skin cancer. Therefore normally organic filtering substances are used, which because of their chemical structure are able to absorb ultraviolet light. Through the uptake of the UV-radiation electrons in the filter molecule are brought into an excited state. The energy which thereby is taken up is thereafter again set free as radiation of heat, whereby photosensitive molecules are going back into their energetic ground state, whereas in the case of photoinsensitive filters, to which the bigger part of the known light protection factors belong, a chemical change occurs, such as e.g. an isomerization or a radical degradation. In addition to the not always satisfactory photostability of the light protection factors, another problem resists in that the filtersxe2x80x94also in cosmetic oilsxe2x80x94only have a limited solubility, respectively dispersing ability. Thereby it can happen that the substances during storage precipitate or sediment, whereby the light protection preparation looses a substantial part of its efficiency.
In this connection reference is made to the European patent EP-B1 0500718 (Donzis), from which the use of glucans in sun protecting agents is known. The glucans are obtained through extraction from the cell walls of yeasts, they are insoluble in water and contain (1,6) linkages. Further in EP-A1 0681830 (Unilever) sun protection agents are suggested which contain ethylene/vinyl acetate copolymers and polyacrylates, UV light protection filters and possibly also up to 10% by weight of glucans.
Therefore the task of the present invention was to improve both the oil solubility and the oil dispersability of UV light protection factors, and also their photosensitivity. Further preparations should be made available which compared to the products according to known art should be distinguished through immune modulating or immune stimulating properties, improved adhesion, film forming abilities and water resistance.
The object of the invention is sun protection agents, containing
(a) water soluble xcex2-(1,3) glucans, substantially free from xcex2-(1,6)-bonds, and
(b) UV light protection factors.
Surprisingly it was found that the addition of xcex2-(1,3) glucans, which are substantially free from xcex2-(1,6) linkages not only increase the solubility or dispersability of UV light protection factors in cosmetic oils, but also vitally improve their photosensitivity, whilst glucans, which are insoluble in water, and which have noteworthy contents of xcex2-(1,6) links, show no effect both in direction of solubilisation and in direction of photosensitivity. The invention comprises the perception that the agents stimulate the immune system and have an improved adhesion, film formation and water resistance.
The term glucans is intended to mean homopolysaccharides based on glucose. Depending on sterical linking there is a difference between xcex2-(1,3), xcex2-(1,4) and xcex2-(1,6) glucans. xcex2-(1,3) Glucans normally show a helical structure, whereas glucans with a (1,4) linkage generally have a linear structure. The xcex2-glucans of the invention have a (1,3) structure, i.e. they are substantially free from undesired (1,6) linkages. Preferably such xcex2-(1,3) glucans are used where the side chains exclusively show (1,3) linkages. Especially the agents contain glucans which are obtained on the basis of yeast from the family Sacchaomyces, especially Saccharomyces cerevisiae. Glucans of this type are available in technical amounts according to known methods. The international patent application WO 95/30022 (Biotec-Mackzymal) describes e.g. a method for producing such substances, wherein glucans with xcex2-(1,3) and xcex2-(1,6) linkages are brought in contact with xcex2-(1,6) glucanases in such a way, that practically all xcex2-(1,6) linkages are loosened. Preferably used for the manufacture of these glucans are glucanases based on Trichodermia harzianum. As to the manufacture and availability of the glucans contained in these agents, reference is made to the above cited publication.
UV light protection factors are e.g organic substances (light protection filters) which by room temperature are in liquid or crystalline form, and which are capable of absorbing ultraviolet radiation and to give free the received energy in the form of radiation with long wavelength, e.g. in the form of heat. UVB filters can be soluble in oils or in water. As oil soluble substances the following are mentioned as examples:
3-Benzyliden camphor, respectively 3-benzylidene norcamphor and the derivatives thereof, e.g. 3-(4-methylbenzylidene) camphor as described in EP-B1 0693471;
4-aminobenzoic acid derivatives, preferably 4-(dimethylamino) benzoic acid 2-ethylhexylester, 4-(dimethylamino) benzoic acid 2-octylester and 4-(dimethylamino) benzoic acid amylester;
esters of cinnamonic acid, preferably 4-methoxy cinnamoic acid 2-ethylhexylester, 4-methoxy cinnamoic acid propylester, 4-methoxy cinnamoic acid isoamylester, 2-cyano-3,3-phenyl cinnamoic acid 2-ethythexylester (octocrylene);
esters of salicylic acid, preferably salicylic acid 2-ethylhexylester, salicylic acid 4-isopropyl benzylester, salicylic acid homomenthylester;
derivatives of benzophenone, preferably 2-hydroxy-4-methoxy benzophenone, 2-hydroxy-4-methoxy-4xe2x80x2-methyl benzophenone, 2,2xe2x80x2-dihydroxy-4-methoxy benzophenone;
esters of benzalmalonic acid, preferably 4-methoxy benzmalonic acid 2-ethylhexyl ester,
triazine derivatives, such as e.g. 2,4,6-trianilino-(p-carbo-2xe2x80x2-ethyl-1xe2x80x2-hexyloxy)-1,3,5-triazine and octyltriazone, as described in EP A1 0818450;
propane-1,3-diones, such as e.g. 1-(4-tert.-butylphenyl)-3-(4xe2x80x2-methoxyphenyl)-propane-1,3-dion;
ketotricyclo(5,2,1,0)-decane derivatives, as described in EP-B1 06945521.
As water soluble substances can be mentioned:
2-Phenylbenzimidazol-5-sulfonic acid and the alkali, aalkaline earth, ammonium, alkylammonium, alkanolammonium and glucammonium salts;
sulfonic acid derivatives of benzophenones, preferably 2-hydroxy-4-methoxybenzophenon-5-suflfonic acid and their salts;
sulfonic acid derivatives of 3-benzylidencamphen, such as e.g. 4-(2-oxo-3-bomylidenmethyl)-benzolsulfonicc acid and 2-methyl-5-(2-oxo-bornyliden)-sulfonic acid and their salts.
As typical UV-A filter especially derivatives of benzoyl methane comes in question, such as e.g. 1-(4xe2x80x2-tert.-butylphenyl)-3-(4xe2x80x2-methoxyphenyl)propane-1,3-dion, 4-tert.butyl-4xe2x80x2-methoxydibenzoyl-methan (Parsol 1789), or 1-phenyl-3-(4xe2x80x2-isopropylphenyl-propane-1,3-dion. The UV-A and UV-B filters of course also can be used in mixtures. In this case combinations of octocrylene or camphor derivatives with butyl methoxydibenzoylmethane are especially photosensitive.
In addition to the mentioned soluble substances also insoluble light protection pigments can be used for this purpose, i.e. fine disperse metal oxides or salts. Examples of suitable metal oxides are especially zinc oxide and titanium dioxide and in addition other oxides of iron, zirconium, silicon, manganese, aluminium and cerium, as well as their mixtures. As salts silicates (talk), barium sulphate or zinc stearate can be used. The oxides and salts are used in form of the pigments for skin caring and skin protecting emulsions and decorative cosmetics. The particles should have an average diameter of less than 100 nm, preferably between 5 and 50 nm and especially between 15 and 30 nm. They can have a spherical shape, but particles can also be used which have an ellipsoidal form or else have a shape which differs from the spherical shape. In sun protecting agents preferably so-called micro or nano pigments are used. Preferably micronized zinc oxide is used.
Further suitable UV light protection factors can be found in the survey by P. Finkel in Sxc3x96SFW-Journal 122, 543 (1996). Likewise suitable are herbal extracts with UV absorbing or antioxidative properties. In a preferable version of the invention the agents contain
(a) 0.01 to 25, preferably 0.5 to 15 and especially 1 to 5% by weight of water soluble xcex2-(1,3) glucans, which are substantially free from xcex2-(1,6) linkages, and
(b) 0.05 to 10, preferably 0.5 to 8 and especially 1 to 5% by weight of UV light protection factors,
provided that the stated amounts are filled up to 100% by weight with water as well as where appropriate further auxiliary and additional substances.
The addition of xcex2-(1,3) glucans, which are substantially free from xcex2-(1,6) linkages, not only improves the solubility or dispersability of UV light protection factors in cosmetic oils, but also increase their photosensitivity. Another object of the invention is therefore the use of the mentioned substances for improvement of the photostability and solubility of UV light protection factors in sun protecting agents.
The sun protection agents according to the invention, such as for example cremes, lotions, oils, gels, sticks and suchlike, can further as additional auxiliary and additional agents contain mild surfactants, oil bodies, emulsifiers, hyperfatting agents, pearl lustre waxes, consistency substances, thickening agents, polymers, silicone compounds, fats, waxes, stabilizing agents, biogenic active substances, deodorants, agents against dandruff, film forming agents, swelling agents, antioxidants, inorganic color pigments, hydrotropes, preservatives, insect repellents, self tanning agents, solubilizing agents, perfume oils, colouring agents and suchlike.
Typical examples of suitable mild, i.e. especially skin compatible surfactants are fatty alcohol polyglycol ether sulphates, monoglyceride sulphates, mono- and/or dialkyl sulfosuccinates, fatty acid isethionates, fatty acid sarcosinates, fatty acid taurides, fatty acid glutamates, xcex1-olefin sulphonates, ethercarboxylic acids, alkyl oligoglucosides, fatty acid glucamides, alkylamido betaines and/or protein fatty acid condensates, the last mentioned preferably based on wheat proteins.
As oil bodies use can be made of for example Guerbet alcohols based on fatty alcohols with 6 to 18, preferably 8 to 10 carbon atoms, esters of linear C6-C22 fatty acids with linear C6-C22 fatty alcohols, esters of branched C6-Cl3 carboxylic acids with linear C6-C22 fatty alcohols, such as e.g. myristyl myristate, myristyl palmitate, myristyl stearate, myristyl isostearate, myristyl oleate, myristyl behenate, myristyl erucate, cetyl myristate, cetyl palmitate, cetyl stearate, cetyl isostearate, cetyl oleate, cetyl behenate, cetyl erucate, stearyl myristate, stearyl palmitate, stearyl stearate, stearyl isostearate, stearyl oleate, stearyl behenate, stearyl erucate, isostearyl myristate, isostearyl palmitate, isostearyl stearate, isostearyl isostearate, isostearyl oleate, isosteayl behenate, isostearyl oleate, oleyl myristate, oleyl palmitate, oleyl stearate, oleyl isostearate, oleyl oleate, oleyl behenate, oleyl erucate, behenyl myristate, behenyl palmitate, behenyl stearate, behenyl isostearate, behenyl oleate, behenyl behenate, behenyl erucate, erucyl myristate, erucyl palmitate, erucyl stearate, erucyl isostearate, erucyl oleate, erucyl behenate and erucyl erucate. In additon esters of linear C6-C22 fatty acids with branched alcohols, especially 2-ethylhexanol, esters of hydroxycarboxylic acids with linear or branched C6-C22 fatty alcohols, especially dioctyl malate, esters of linear and/or branched fatty acids with polyvalent alcohols (such as e.g. propylene glycol, dimeric diol or trimeric triol) and/or Guerbet alcohols, triglycerides based on C6-C10 fatty acids, liquid mixtures of mono-/di-/triglycerides based on C6-C18 fatty acids, esters of C6-C22 fatty alcohols and/or Guerbet alcohols with aromatic carboxylic acids, especially benzoic acid, esters of C2-C12 dicarboxylic acids with linear or branched alcohols with 1 to 22 carbon atoms or polyols with 2 to 10 carbon atoms and 2 to 6 hydroxyl groups, plant oils, branched primary alcohols, substituted cyclohexanes, linear and branched C6-C22 fatty alcohol carbonates, Guerbet carbonates, esters of benzoic acid with linear and/or branched C6-C22 alcohols (e.g. Finsolv(copyright) TN), linear or branched, symmetrical or unsymmetrical dialkyl ethers with 6 to 22 carbon atoms in each alkyl group, ring opening products of epoxydated fatty acid esters with polyols, silicone oils and/or aliphatic or naphthenic hydrocarbons, such as e.g. squalan, squalen or dialkyl cyclohexanes, can be used
As emulsifiers for example nonionic surfactants from at least one of the following groups may be used:
(1) Addition products of 2 to 30 moles ethylene oxide and/or 0 to 5 moles propylene oxide on linear fatty alcohols with 8 to 22 C atoms, on fatty acids with 12 to 22 C atoms and on alkyl phenols with 8 to 15 C atoms in the alkyl group;
(2) C12/18 fatty acid mono- and -diesters of addition products of 1 to 30 moles ethylene oxide and glycerol;
(3) glycerol mono- and diesters and sorbitan mono- and diesters of saturated and unsaturated fatty acids with 6 to 22 carbon atoms and their ethylene oxide addition products;
(4) alkyl mono- and oligoglycosides with 8 to 22 carbon atoms in the alkyl group and their ethoxylated analogues;
(5) addition products of 15 to 60 moles ethylene oxide on ricinus oil and/or hardened ricinus oil;
(6) polyol and especially polyglycerol esters, such as e.g. polyglycerol polyricinoleate, polyglycerol poly-12-hydroxystearate or polyglycerol dimerate isostearate, and also mixtures of compounds from more of these classes of substances;
(7) addition products of 2 to 15 moles ethylene oxide on ricinus oil and/or hardened ricinus oil;
(8) partial esters based on linear, branched, unsaturated or saturated C6/22 fatty acids, ricinolic acid and 12-hydroxy stearic acid and glycerol, polyglycerol, pentaerythrite, dipentaerythrite, sugar alcohols (e.g. sorbitol), alkyl glucosides (e.g. methyl glucoside, butyl glucoside, lauryl glucoside) as well as polyglucosides (e.g. cellulose);
(9) mono-, di- and trialkylphosphates as well as mono-, di- and/or tri-PEG alkylphosphates and their salts;
(10) wool wax alcohols;
(11) polysiloxane/polyalkyl/polyether copolymers or corresponding derivatives;
(12) mixed esters of pentaerythrite, fatty acids, citric acid and fatty alcohol according to DE 1165574 PS and/or mixed esters of fatty acids with 6 to 22 carbon atoms, methyl glucose and polyols, preferably glycerol or polyglycerol,
(13) polyalkylene glycols, as well as
(14) glycerol carbonate.
The addition products of ethylene oxide and/or of propylene oxide on fatty alcohols, fatty acids, alkyl phenols, glycerol mono- and diesters as well as sorbitan mono- and -diesters of fatty acids or on ricinus oil are known products which are commercially available. They are mixtures of homologous substances, with average degree of alkoxylation corresponding to the ratio of the amounts of the substances ethylene oxide and/or propylen oxide and substrate, with which the addition reaction is carried out. C12/18 fatty acid mono- and -diesters of addition products of ethylene oxide on glycerol are known from DE 2024051 PS as revertive fatting agents for cosmetic preparations.
C8/18 alkyl mono- and oligoglycosides, their manufacture and their use is known from prior art. Their preparation can especially be carried out by reaction of glucose or oligosaccharides with primary alcohols having 8 to 18 C atoms. With regard to the glycoside residue both monoglycosides, where a cyclic sugar group is glycosidic bond to the fatty alcohol, and oligomeric glycosides with a degree of oligomerisation until preferably about 8, are suitable. The degree of oligomerization is then a statistical mean value, based on a distribution of homologues which is usual for such products of technical quality.
Zwitterionic surfactants can also be used as emulsifiers. The term zwitterionic surfactants is intended to mean such surface active compounds which in their molecule have at least a quatenary ammonium group and at least one carboxylate and one sulphonate group. Especially suitable zwitterionic surfactants are the so-called betaines such as the N-alkyl-N,N-dimethyl ammonium glycinates, for example the coco alkyldimethyl ammonium glycinate, N-acylaminopropyl-N,N-dimethyl ammonium glycinate, for example the coco acylaminopropyl dimethyl ammonium glycinate, and 2-alkyl-3-carboxylmethylhydroxyethyl imidazoline with in each case 8 to 18 C atoms in the alkyl or acyl-groups, as well as the coco acylaminoethyl hydroxyethylcarboxymethyl glycinate. Especially preferred is that under the CTFA term cocamidopropyl betaine known fatty acid amide derivative. Also suitable emulsifiers are ampholytic surfactants. Ampholytic surfactants are such surface active compounds which in addition to a C8/18 alkyl or acyl group in the molecule at least contain a free amino group and at least one xe2x80x94COOH or xe2x80x94SO3H group and which can form inner salts. Examples of suitable ampholytic surfactants are N-alkyl glycines, N-alkyl propionic acids, N-alkyl aminobutyric acids, N-alkyl iminodipropionic acids, N-hydroxyethyl-N-alkylamidopropyl glycines, N-alkyltaurines, N-alkylsarcosines, 2-alkylaminopropionic acids and alkylamino acetic acids with in each case about 8 to 18 C atoms in the alkyl group. Especially preferable ampholytic surfactants are the N-coco alkylamino propionate, the coco acylamino ethylaminopropionate and the C12/18 acylsarcosine. In addition to the ampholytic, also quaternary emulsifiers can be used, of which ester salts of the type of esterquats, preferably methylquatemised di-fatty acid triethanolamine ester salts, are especially preferable.
As hyperfatting agents substances such as for example lanolin and lecithin as well as polyethoxylated or acylated lanolin and lecithin derivatives, polyol fatty acid esters, monoglycerides and fatty acid alkanolamides can be used, whereby the last mentioned at the same time act as foam stabilisers.
As exemplary pearl gloss waxes the following should be mentioned: Alkylene glycolester, especially ethyleneglycol distearate; fatty acid alkanolamides, especially coco fatty acid diethanolamide; partial glycerides, especially stearic acid monoglyceride; esters of polyvalent, possibly hydroxysubstituted carboxylic acids with fatty alcohols with 6 to 22 carbon atoms, especially long chain esters of tartaric acid; fat substances, such as for example fatty alcohols, fatty ketones, fatty aldehydes, fatty ethers and fatty carbonates, wherin the sum of carbon atoms is at least 24, especially lauron and distearyl ethers; fatty acids such as stearic acid, hydroxystearic acid or behenic acid, ring opening products of olefin epoxides with 12 to 22 carbon atoms with fatty alcohols with 12 to 22 carbon atoms and/or polyols with 2 to 15 carbon atoms and 2 to 10 hydroxyl groups as well as their mixtures.
As consistency givers preferably use is made of fatty alcohols or hydroxy fatty alcohols with 12 to 22 and preferably 16 to 18 carbon atoms and additionally partial glycerides, fatty acids or hydroxy fatty acids. A combination of these substances with alkyl oligoglucosides and/or fatty acid-N-methyl glucamides with the same chain length and/or polyglycerol-poly-12-hydroxy stearates.
Suitable thickening agents are for example types of aerosil (hydrophilic silicic acids), polysaccharides, especially xanthan gum, guar-guar, agar-agar, alginates and tyloses, carboxymethyl celluloses and hydroxyethyl celluloses, as well as higher molecular polyethylenglycol mono- and diesters of fatty acids, polyacrylates, (e.g. Carbopols(copyright) from Goodrich or Synthalenes(copyright) from Sigma), polyacrylamides, polyvinyl alcohol and polyvinyl pyrrolidone, surfactants such as for example ethoxylated fatty acid glycerides, ester of fatty acids with polyols such as for example pentaerythrite or trimethylolpropane, fatty alcohol ethoxytates with narrow distribution of homologous or alkyl oligoglucosides as well as elektrolytes such as sodium chloride and ammonium chloride.
Suitable cationic polymers are for example cationic cellulose derivatives, such as e.g. a quaternized hydroxyethyl cellulose, which is available under the name of Polymer JR 400(copyright) from Amerchol, cationic starch, copolymers of diallyl ammonium salts and acrylamides, quaternized vinylpyrrolidone/vinylimidazol polymers, such as e.g. Luviquat(copyright) (BASF), condensation products of polyglycols and amines, quaternized collagen polypeptides, such as for example lauryl dimonium hydroxypropyl hydrolyzed collagen (Lamequate(copyright)/Grxc3xcnau), quaternized wheat polypeptides, polyethyleneimine, cationic silicone polymers, such as e.g. amidomethicones, copolymers of adipic acid and dimethylamino hydroxypropyl diethylenetriamine (Cartaretine(copyright)/Sandoz), copolymers of acrylic acid with dimethyl diallylammonium chloride (Merquate(copyright) 550/Chemviron), polyamino polyamides, such as e.g. described in FR 2252840 A, as well as their cross-linked water soluble polymers, cationic chitin derivatives such as for example quaternized chitosane, possibly micro crystalline distributed, condensation products of dihalogen alkyls, such as e.g. dibromobutane with bisdialkylamines, such as e.g. bis-dimethylamino-1,3-propane, cationic guar-gum, such as e.g. Jaguar(copyright) CBS, Jaguar(copyright) C-17, Jaguar(copyright) C-16 from Celanese, quatemised ammonium salt polymers, such as e.g. Mirapol(copyright) A-15, Mirapol(copyright) AD-1, Mirapol(copyright) AZ-1 from Miranol.
As exemplary anionic, zwitterionic, amphoteric and non-ionic polymers the following can be used: Vinyl acetate/crotonic acid copolymers, vinyl pyrrolidone/vinyl acrylate copolymers, vinyl acetate/butyl maleate/isobomyl acrylate copolymers, methyl vinylether/maleic acid anhydride copolymers and their esters, non-cross-linked and with polyols cross-linked polyacrylic acids, acrylamido propyltrimethyl ammonium chloride/acrylate copolymers, octylacrylamide/methyl methacrylate/tert.-butylaminoethyl methacrylate/2-hydroxypropyl methacrylate copolymers, polyvinylpyrrolidone, vinylpyrrolidone/vinylacetate copolymers, vinylpyrrolidon/dimethylamino ethylmethacrylate/vinyl caprolactam terpolymers as well as possibly derivatized cellulose ethers and silicones.
Suitable silicon compounds are for example dimethyl polysiloxane, methylphenyl polysiloxane, cyclic silicones as well as amino, fatty acid, alcohol, polyether, epoxy, fluorine, glykoside and/or alkyl modified silicon compounds, which at room temperatur can be in the liquid as well as in the resin state. Further suitable are simethicones, which are mixtures of dimethicones with an average chain length of 200 to 300 dimethyl siloxane units and hydrogenated silicates. A detailed survey of suitable volatile silicones can also be found in Todd et al., Cosm. Toil. 19, 27 (1976).
Typical exemplary fats are glycerides, and as waxes natural waxes among others, can be used, such as e.g. candelilia wax, carnauba wax, Japan wax, espartogras wax, cork wax, guaruma wax, rice seed oil wax, sugar cane wax, ouricury wax, montan wax, beeswax, schellak wax, spermaceti, lanolin (wool wax), burzel fat, ceresin, ozokerit (terrestrial wax), petrolatum, paraffin waxes, micro waxes; chemically modified waxes (hard waxes), such as e.g. montanester waxes, sasot waxes, hydrogenated yoyoba waxes as well as synthetic waxes, such as e.g. polyalkylene waxes and polyethylene glycol waxes.
As stabilizers metal salts of fatty acids, such as e.g. magnesium, aluminium and/or zinc stearate or ricinoleate can be used.
As biogenic active substances should be understood for example tocopherol, tocopherol acetate, tocopherol palmitate, ascorbic acid, desoxy ribonucleic acid, retinol, bisabolol, allantoin, phytantriol, panthenol, AHA acids, aminoacids, ceramides, pseudoceramides, essential oils, extracts of plants and vitamin complexes.
As deo active agents e.g. antiperspirants such as aluminium chlorohydrate come into question. This agent is in the form of colourless, hygroscopic crystals, which easily melt in air, and is obtained through evaporation of solutions of aluminium chloride in water. Aluminium chlorohydrate is used for manufacturing of perspiration inhibiting and deodorising preparations and has probably its effect through the partial closure of the perspiratory gland by means of precipitation of proteins and/or polysaccharides [see J. Soc. Cosm. Chem. 24 281 (1973)]. Under the trade name Locron(copyright) of Hoechst AG, Frankfurt/FRG, an aluminium chlorohydrate is for example on the market, which corresponds to the formula [Al2(OH)5Cl]xc2x72.5 H2O, and use of this is especially preferred (see J. Pharm. Pharmacol. 26 531 (1975)]. In addition to the chlorohydrates also aluminium hydroxylactates as well as acid aluminium/zirconium salts can be used. As further deo active agents esterase inhibitors can be added. These are preferably trialkyl citrates such as trimethyl citrate, tripropyl citrate, triisopropyl citrate, tributyl citrate and especially triethyl citrate (Hydagen(copyright) CAT, Henkel KGaA, Dusseldorf/FRG). The substances inhibit the enzyme activity and thereby reduce the formation of odours. Probably the free acid is thereby set free through the cleavage of the citric acid ester, and this acid lowers the pH value of the skin so much that the enzymes thereby are inhibited. Further substances which can be used as estersase inhibitors are sterol sulphates or phosphates, such as for example lanosterol, cholesterol, campesterol, stigmasterol and sitosterol sulphate or phosphate, Dicarboxylic acids and their esters, such as for example glutaric acid, glutaric acid monoethylester, glutaric acid diethylester, adipic acid, adipic acid monoethylester, adipic acid diethylester, malonic acid and malonic acid diethylester, hydroxycarboxylic acids and their esters, such as for example citric acid, malic acid, tartaric acid or tartaric acid diethylester. Antibacterial active substances, which influence the germ flora and kill sweat destroying bacterias or inhibit their growth, can also be contained in the pin preparations. Examples of this are chitosan, phenoxyethanol and chlorohexidin gluconate. Also 5-chloro-2-(2,4-dichlorophen-oxy)-phenol has shown to have an especially good effect, and this product is marketed under the trade name Irgasan(copyright) by Ciba-Geigy, Basel/CH.
As anti dandruff agents climbazol, octopirox and zinc pyrethion can be used. Useable film formation agents are for example chitosan, microcrystalline chitosan, quaternary chitosan, polyvinylpyrrolidon, vinylpyrrolidon/vinylacetate copolymers, polymers of the acrylic acids, quaternary derivatives of cellulose, collagen, hyaluronic acid or its salts and similar compounds. As swelling agents for aqueous phases montmorillonite, clay mineral substances, pemulen, as well as alkyl modified Carbopol types (Goodrich) can be used. Further suitable polymers or swelling agents can be found in the survey of R. Lochhead in Cosm. Toil. 108, 95 (1993).
In addition to the primary light protection substances also secondary light protection substances of the antioxidant type find use, which interrupt the photochemichal reaction chain, which is initiated when UV radiation penetrates the skin. Typical examples of such are amino acids (e.g. glycin, histidin, tyrosin, tryptophan) and their derivatives, imidazoles (e.g. urocaninic acid) and their derivatives, peptides such as D,L-camosine, D-camosine, L-camosine and their derivatives (e.g. anserine), carotinoides, carotine (e.g. xcex1-carotin, xcex2-carotin, lycopin) and their derivatives, chlorogenic acid and its derivatives, liponic acid and its derivatives (e.g. dihydroliponic acid), aurothioglucose, propylthiouracil and other thiols (e.g. thioredoxin, glutathion, cystein, cystin, cystamine and their glycosyl, n-acetyl, methyl, ethyl, propyl, amyl, butyl and lauryl, palmitoyl, oleyl, xcex3-linoleyl, cholesteryl and glyceryl esters) as well as their salts, dilauryl thiodipropionate, distearyl thiodipropionate, thiodipropionic acid and their derivatives (esters, ethers, peptides, lipides, nucleotides, nucleosides and salts) as well as sulfoximine compounds (e.g. buthionin sulfoximines, homocystein sulfoximines, butionin sulfones, penta-, hexa-, hepta-thionin sufoximine) in very small compatible doses (e.g. pmol to xcexcmol/kg), further (metal) chelating agents (e.g. xcex1-hydroxy fatty acids, palmitic acid, phytinic acid, lactoferrine), xcex1-hydroxy acids (e.g. citric acid, lactic acid, malic acid), humin acid, gallic acid, gallic extracts, bilirubin, bifiverdin, EDTA, EGTA and their derivatives, unsaturated fatty acids and their derivatives (e.g. xcex3-linolenic acid, linolic acid, oleic acid), folic acid and their derivatives, ubichinon and ubichinol and their derivatives, vitamin C and derivatives (e.g. ascorbyl palmitate, Mg-ascorbyl phosphate, ascorbyl acetate), tocopheroles and derivatives (e.g. vitamin E acetate), vitamin A and derivatives (vitamin A patmitate) as well as koniferyl benzoate of benzoe resin, rutinic acid and their derivatives, xcex1-glycosylrutin, ferula acid, furfuryliden glucitol, carnosine, butylhydroxy toluene, butylhydroxy anisol, nordihydro guajak resin acid, nordihydro guajaret acid, trihydroxy butyrophenon, uric acid and their derivatives, mannose and its derivatives, super oxide dismutase, zinc and its derivatives (e.g. ZnO, ZnSO4), selen and its derivatives (e.g. selen-methionin), stilbenes and their derivatives (e.g. stilben oxide, trans-stilben oxide) and the derivatives suitable according to the invention (salts, esters, ethers, sugars, nucleotides, nucleosides, peptides and lipids) of these mentioned active substances.
For improvement of the flow properties further hydrotropes, such as for example ethanol, isopropyl alcohol, or polyols can be used. Polyols which in this case can be used preferably have 2 to 15 carbon atoms and at least two hydroxyl groups. The polyols can further contain additional functional groups, especially amino groups, or be modified with nitrogen. Typical examples are:
Glycerol;
alkylen glycols, such as for example ethylene glycol, diethylene glycol, propylene glycol, butylene glycol, hexylene glycol as well as polyethylen glycols with an average molecular weight from 100 to 1000 Daltons;
oligoglycerol mixtures of technical quality with a self-condensation degree of 1.5 to 10, such as e.g. technical quality diglycerol mixtures with a diglycerol content of 40 to 50% by weight;
menthol compounds, such as especially trimethylol ethane, trimethylol propane, trimethylol butane, pentaerythrite and dipentaerythrite;
low alkyl glucosides, especially such with 1 to 8 carbons in the alkyl residue, such as for example methyl and butyl glucoside;
sugar alcohols with 5 to 12 carbon atoms, such as for example sorbitol or mannit;
sugars with 5 to 12 carbon atoms, such as for example glucose or saccharose;
aminosugars, such as for example glucamine;
dialcoholamines, such as diethanolamine or 2-amino-1,3-propanediol.
As preservatives for example phenoxyethanol, formaldehyde solution, parabene, pentanediol or sorbic acid as well as those mentioned in enclosure 6, parts A and B of the cosmetic regulation, are further classes of substances. As insect repellents N,N-diethyl-m-toluamide, 1,2-pentanediol or insect repellent 3535 come into question, as self tanning agent dihydroxyaceton is suited.
As perfume oils mixtures of natural and synthetic scent substances should be mentioned. Natural scent substances are extracts of flowers (lilies, lavendel, roses, jasmin, neroli, ylang-ylang), stems and blades (geranium, patchouli, petitgrain), fruits (anis, coriander, caraway, juniper), fruit shells (bergamot, lemon, orange), roots (macis, angelica, celery, kardamon, costus, iris, calmus), wood (stone pine, sandel, guajac, cedar, rosewood), herbs and grass (tarragon, lemongrass, sage, thyme), needles and twigs (spruce, fir, pine, traipsed), resins and balsams (galbanum, elemi, benzoe, myrrh, olibanum, opoponax). Raw materials from animals are also possible, such as for example zibet and castoreum. Typical synthetic odour compounds are products from types of esters, ethers, aldehydes, ketones, alcohols and hydrocarbons. Odour compounds from types of esters are e.g. benzyl acetate, phenoxyethyl isobutyrate, p-tert.-butylcyclohexyl acetate, linalyl acetate, dimethylbenzylcarbinyl acetate, phenylethyl acetate, linalyl benzoate, benzyl formate, ethylmethylphenyl glycinate, allylcyclohexyl propionate, styrallyl propionate and benzyl salicylate. Benzylethyl ether belongs for example to the ethers, to the aldehydes e.g. the linear alkanales with 8 to 18 carbon atoms, citral, citronellal, citronellyl oxyacetaldehyde, cyclamen aldehyde, hydroxy citronellal, lilial and bourgeonal, to the ketones e.g. the ionones, xe2x88x9d-isomethyl ionon and methylcedryl ketone, to the alcohols anethol, citronellol, eugenol, isoeugenol, geraniol, linalool, phenylethyl alcohol and terpineol; to the hydrocarbons mainly the terpenes and balsams belong. However, mixtures of different odour substances are preferred, which together give a pleasant smell. Also etheral oils with low volatility, which often are used as aroma components, are suited as perfume oils, e.g. sage oil, chamomile oil, carnation oil, melissa oil, mint oil, cinnamon leaf oil, limeflower oil, juniper berry oil, vetiver oil, oliban oil, galbanum oil, labolanum oil and lavandin oil. Preferably used are bergamot oil, dihydromyrcenol, lilial, lyral, citronellol, phenylethyl alcohol, xcex1-hexylcinnamon aldehyde, geraniol, benzylaceton, cyclamen aldehyde, linalool, boisambrene forte, ambroxane, indol, hedione, sandelice, lemon oil, mandarin oil, orangenoil, allylamyl glycolate, cyclovertal, lavandine oil, muskateller sage oil, xcex2-damascone, geranium oil bourbon, cyclohexyl salicylate, vertofix coeur, iso-E-super, fixolide NP, evemyl, iraidein gamma, phenylacetic acid, geranyl acetate, benzyl acetate, rose oxide, romillate, irotyl and floramate, alone or in mixtures.
As colouring agents such substances which are suited and approved for cosmetic purposes can be used, such as for example those mentioned in the publication xe2x80x9cKosmetische Fxc3xa4rbemittelxe2x80x9d (cosmetic dyes) of the xe2x80x9cFarbstoffkommission der Deutschen Forschungsgemeinschaftxe2x80x9d, published by Verlag Chemie, Weinheim, 1984, p. 81-106. These dyes are generally used in concentrations from 0.001 to 0.1% by weight, based on the whole mixture.
Typical examples of germ inhibiting substances are preservatives with specific effects against gram-positive bacteria, such as 2,4,4xe2x80x2-trichloro-2xe2x80x2-hydroxy diphenylether, chlorohexidin (1,6-di-(4-chlorophenyl-biguanido-hexan) or TCC (3,4,4xe2x80x2-trichlorocarbanilide). Many scent substances and etheral oils also have antimicrobial properties. Typical examples are the active agents eugenol, menthol and thymol in carnation, mint and thyme oil. An interesting natural deo substance is the terpene alcohol famesol (3,7,11-trimethyl-2,6,10-dodecatrien-1-ol), which is present in lime flower oil and has a smell of lilies of the valley. Also glycerol monolaurate have been used as bacteriostaticum. Normally the content of the further germ inhibiting agent is about 0.1 to 2% by weightxe2x80x94based on the solids content of the preparations.
The cumulative contents of the auxiliary and additional agents can be 1 to 50, preferably 5 to 40% by weight, based on the agents. The manufacture of the agents can take place by common cold or hot processes; preferably the work is carried out according to the phase inversion temperature method.


A three-dimensional semiconductor device may include a substrate including a cell array region, a word line contact region, and a peripheral circuit region, gate electrodes stacked on the substrate to extend from the cell array region to the word line contact region, a channel hole penetrating the gate electrodes on the cell array region and exposing an active region of the substrate, a dummy hole penetrating the gate electrodes on the word line contact region and exposing a device isolation layer provided on the substrate, and a semiconductor pattern provided in the channel hole but not in the dummy hole.

Example embodiments of the inventive concepts relate to a semiconductor device and a method of fabricating the same, and in particular, to a three-dimensional semiconductor device and a method of fabricating the same.
The continued development of highly integrated semiconductor devices is spurred in part by consumer demand for low-cost, superior performance products. Indeed, particularly in the case of semiconductor devices, increased device integration is a major factor in achieving price points satisfying market demands. Conventionally, semiconductor memory devices include planar or two-dimensional (2D) memory cell arrays, i.e., memory cell arrays having memory cells laid-out in a two-dimensional plane. Further integration of such devices is becoming more difficult (and costly) as patterning technologies approach practical limits. At the very least, prohibitively expensive process equipment would be needed to achieve major advances in 2D memory cell array device integration.
As a result, three-dimensional (3D) semiconductor devices have been proposed in which the memory cells of the memory cell array are arranged in three dimensions. However, there are significant manufacturing obstacles in achieving low-cost, mass-production of 3D semiconductor devices, particularly in the mass-fabrication of 3D devices that maintain or exceed the operational reliability of their 2D counterparts.

Semiconductor device and method of fabricating the same