text:
|Publication number
|Publication type
|Application number
|Publication date
|Jun 3, 2003
|Filing date
|Feb 26, 2002
|Priority date
|Sep 7, 1999
|Fee status
|Also published as
|Publication number
|Lawrence D. Rosenthal
|Original Assignee
|Lawrence D. Rosenthal
|Export Citation
|BiBTeX, EndNote, RefMan
|Patent Citations (24), Non-Patent Citations (1), Referenced by (64), Classifications (20), Legal Events (3)
|External Links: USPTO, USPTO Assignment, Espacenet
This application is a division of U.S. application Ser. No. 09/653,388, filed Sep. 1, 2000, now issued as U.S. Pat. No. 6,366,202, and also claims benefit of U.S. provisional application, Serial No. 60/152,691, filed Sep. 7, 1999.
The invention relates generally to systems for finding lost objects. In particular, the invention relates to paired devices, particular those employing acoustic search signals, for finding the lost one of the pair.
It is common in personal and business life to lose small items in a relatively small area. A common example is a set of personal keys including keys for a personal automobile and probably for home and business. Automobile manufactures invariably supply duplicate sets of keys. The car owner usually carries one set in a pocket or purse and leaves the other set in a known location such as a key rack or storage container. If the primary set is misplaced, typically in process of changing clothes or emptying pockets or purses, the other, secondary set is usually readily available. However, the key owner usually wants to find the primary set, both because of the other keys attached to the key ring but also to assure that the secondary set is not subsequently also lost. Typically, the lost set of keys is known to be in a relatively restricted area, for example, at home in one of two or three rooms, since the lost keys were most probably used to drive home and open the door. Thereafter, their whereabouts in the home may be uncertain. As a result, the search for the missing keys needs to cover only a limited area, but the owner is usually in a rush to leave and wants to find them immediately. Similar limited-area searching is often required for eyeglass cases, television remotes, security badges, and the like.
A lost item finding system may comprise two or more identical or nearly identical locators. Transmission of a search signal from one of the locators causes one or more of the other locators to emit a beacon signal, such as an audible signal and a flashing light, enabling the user to locate the lost locator and attached items. The locators may substantively differ only in a programmed identification code used for either transmitting and/or receiving the search signal.
A preferred embodiment uses an acoustic transducer, for example, a piezoelectric transducer, to receive an acoustic search signal, to transmit a corresponding acoustic search signal, and to transmit an audible beacon signal. In transmission mode, the piezoelectric transducer may be subjected to bipolar pulsing across its two inputs. In reception mode, one input is left floating and connected to amplifying, pulse shaping, and counting circuitry while the other input is held at a fixed potential.
The acoustic transducer may be coupled to a Helmholtz resonant acoustic cavity tuned to the resonant frequency of the piezoelectric element, preferably having an annular output port coupled to a cylindrical cavity. A cap may both define the end of the cavity and be spaced from the case enclosing the cavity to form the annular output port.
Preferably, each locator can be selectively disabled, allowing two locators to perform the responding and beaconing without interference from additional locators.
The acoustic search signaling transmission and detection may be arranged to minimize the effects of ambient noise to allow operation in particularly noisy environments. The search signal may consist of a sequence of tones having well defined frequency differences and separated by quiet periods. The detection of the search signal on one hand may require the detection of a quiet period following the tone sequence but on the other hand may respond to multiple transmissions of the tone sequences in a noisy environment.
The baseline frequency, the first tone of the tone sequence, may preferably be any frequency in a broad range, and the detection circuitry nonetheless can detect the tone sequence by determining the frequency differences of the tones relative to the baseline frequency.
FIG. 1 is a perspective view of one embodiment of the lost item locator of the invention.
FIG. 2 is a schematic representation of the operation of the paired locators of the invention for finding one of them attached to lost items.
FIG. 3 is a simplified schematic diagram of the electronic circuitry usable with an audio embodiment of the invention.
FIG. 4 is a partial plan view of the section of a case of FIG. 1 including the audio transducer cavity.
FIG. 5 is a cross-sectional view of the audio transducer cavity taken along view line 5—5 of FIG. 4.
FIG. 6 is a timing diagram of the sequence of audio tones used for searching.
FIGS. 7 and 8 are flow diagrams of an algorithm usable with the electronic circuitry of FIG. 3 and primarily concerned with the operation of a lost locator receiving a search signal and responding with beacon signals.
FIGS. 9 and 10 are a flow diagrams of an algorithm complementary to those of FIGS. 7 and 8 usable also with the circuitry of FIG. 3 and primarily concerned with operation of an available locator.
FIG. 11 is a schematic diagram of a locator using an RF search signal.
FIG. 1 is a perspective illustration of an embodiment of a locator 10 to be used in the lost item finding system of the invention. The locator 10 includes a molded plastic case 12 enclosing the electronics and audio transducer to be described later. The case 12 is approximately 5 cm long, 3 cm wide, and 1 cm thick so that it can be easily carried in a pocket or purse. The case 12 includes a loop 14 at one corner around which can be wrapped a key ring 16 holding one or more keys 18. However, other items may be attached to the case 12, such as a television remote or security badge among many other possible items which tend to be misplaced. A light emitting diode (LED) 20 protrudes from another comer of the case 12 and selectively emits a visible signal. A switch button 22 attached to a normally open switch is accessible on one flat side 24 of the case for convenient finger activation. A disk-shaped cap 26 is spaced by a small distance from the flat side 24 of the case 12 and is supported thereon by three unillustrated legs. The cap 26 protects an acoustic transducer under it and also forms one side of an acoustic resonator to be described later.
Two such locators 10 a and 10 b illustrated in perspective in FIG. 2 form a lost item finding system. One locator 10 a is assumed to be misplaced along with its attached key or similar item while the other locator 10 b is assumed to be readily available from, for example, a key rack or security box. The attached items are not shown, but they may be the primary and spare key set or a house key and a television remote, either of which is subject to being misplaced. When the user decides that the first locator 10 a and attached item is lost, he finds the second locator 10 b and presses the button 22 with his finger 30. The second locator 10 b emits a coded acoustic signal 34, which is detected by the lost first locator 10 a. In response, the lost first locator 10 a emits another audible acoustic signal 36 and a visible optical signal from its LED 20, which enable the user to locate the lost first locator 10 a. Preferably, the two locators 10 a, 10 b are nearly identical so that either one can be lost and then found by activating the other one.
A simplified schematic diagram of the electronics contained in the case 12 is illustrated in FIG. 3. The illustrated items are soldered to a printed circuit board shaped to fit inside of the case 12. A programmable microprocessor 40, such as a 12C509A available from Microchip Technology, forms the controller of the locator 10. Two serially connected 3V batteries form a DC power supply 42 connected to the power input Vcc of the microprocessor 40 through the LED 20. The microprocessor 40 is designed to operate from a DC power source providing between 3 and 5.5V. In order to provide a voltage in the middle of the operating range, the LED 20 drops the 6V of battery voltage to 4V at the power input Vcc of the microprocessor 40. In sleep mode, the microprocessor 40 consumes only about 1 μA of current while in active mode it consumes about 1 mA of current. The locator 10 stays in sleep mode until its button 22 is activated or it hears an acoustic signal.
The microprocessor 40 has three outputs OUT-1, OUT-2 and OUT-3. The first output OUT-1 connects to a load resistor 44 connected to ground. When the first output OUT-1 goes high, current flows out of the microprocessor 40 through that output, and corresponding additional current flows into the microprocessor power input Vcc through the LED 20 causing it to emit additional light. The second output OUT-2 is connected to the inputs of both a buffer 46 and an inverting tri-state buffer 48, both of which may be formed from a 74HC125 quad tri-state buffer and a resistor. The buffer 46 simply outputs a high-power signal corresponding to its low-power input while the inverting tri-state buffer 48 either outputs a high-power signal inverted from its low-power input or presents a high-impedance output depending upon the signal from the third output OUT-3 from the microprocessor 40. A piezoelectric audio transducer 50, such as available from Murata Electronics, is connected across the outputs of the buffer 46 and the inverting tri-state buffer 48. Assuming that the microprocessor 40 has activated the inverting tri-state buffer 48 with its third output OUT-3, the outputs of the two buffers 46, 48 are complementary, either 0 or 6V, with the polarity determined by the signal from the microprocessor's second output OUT-2. The bipolar signal driving the transducer 50 generates a louder audio signal as the piezoelectric unit is driven in both directions. For audio signaling, this output OUT-2 is switched at a frequency in the range of 5.5 to 7.5 kHz, with the effect that the audio transducer emits an audio signal in this frequency range.
However, in sleep mode or other periods in which the microprocessor 40 is awaiting reception of an audio signal, the microprocessor's third output OUT-3 inactivates the inverting tri-state buffer 48 to its high-impedance output mode and its second output OUT-2 goes low, thus grounding the other side of the audio transducer 50. In this state, the audio transducer 50 can detect an audio signal and convert it to an electrical signal which is amplified by amplifier 52. That is, the transducer 50 can act both as an audio transmitter and audio receiver. The detected audio signal, presumably also at 5.5 to 7.5 kHz, is amplified by amplifier 52 and then filtered by a low-pass filter including a serially connected capacitor 54 and a grounded resistor 56 which removes any DC bias. The audio signal with any DC bias removed is input to a comparator 58 having hysteresis so that any low-level noise is ignored and the generally sinusoidal detected audio signal is converted to a square wave more amenable to digital processing. Each cycle of the square wave amounts to a pulse within the digital circuitry.
The output of the hysteretic comparator 58 is input to a third input IN-3 of the microprocessor 40 and to a divide-by-256 circuit 60, which may be a 74HC393 dual 4-bit counter with the high-order output bit, which changes state every 128 pulses, treated as the output of the divider 60. The divider output is connected to a second input IN-2 of the microprocessor 40. The third microprocessor input IN-3 serves as a received data input that allows the microprocessor 40 to analyze the received audio signal and determine whether the audio signal is from the paired locator seeking to find the lost locator with the illustrated circuitry. The divide-by-256 circuit 60 provides one method of waking up the microprocessor 40 after 128 input pulses of the external audio signal (20 ms for a 6500 Hz signal) have been detected to further determine if the detected audio signal is coded to form a locating signal from the other locator. Using an algorithm to be described in more detail later, if it is determined that a correctly coded audio signal has been received, the microprocessor 40 causes the LED 20 to flash and the audio transducer to emit an audio signal that can be heard by the user.
The circuitry of FIG. 3 does not illustrate common elements, such as transistors, resistors, and capacitors that form the amplifier 52 and power supply leads connected to the non-processor active elements.
The microprocessor 40 is also woken up, if it is asleep, by a low signal applied to its first input IN-1 produced when a normally open switch 62 mechanically connected to the button 22 is closed. The switch 62 is electrically connected between ground and the input IN-1, also serially connected through a resistor 64 and the LED 20 to the power supply 42. When the input IN-1 is activated, the microprocessor 40 causes the audio transducer 50 to emit a coded sequence of audio tones in the range of 5.5 to 7.5 kHz. However, as will be described in reference to the programmed algorithm, the button can be activated in particular ways to cause the locator to perform other functions.
In view of the limited power from small batteries and the possibly noisy ambient environment, it is important that the audio transducer be as efficient as possible both for transmission and reception. The bipolar pulsing with the complementary outputs of the two buffers 46, 48 increases the signal generating ability. Further efficiency is achieved with a Helmholtz resonator similar to that disclosed in the document published by Murata Electronics entitled "Piezoelectric Devices Application Manual," pp. 84-91. As illustrated in the plan view in FIG. 4 and the cross-sectional view of FIG. 5 taken along view line 5—5 of FIG. 4, an upper half case section 70 is formed with a cylindrical cavity 72 between a downwardly projection tubular wall 74 terminating in a sharp annular ridge 76. The piezoelectric transducer 50 includes an integral assembly of a 20 mm brass disk 80, a piezoelectric ceramic layer 82, and a flexible silver electrode layer 84 are fixed to the annular ridge 76 with a flexible adhesive. Unillustrated electrical contacts are made to the brass disk 80 and the silver layer 84 to allow the circuitry of FIG. 3 to apply a voltage across the piezoelectric ceramic layer 82. The resultant lateral contraction or expansion of the piezoelectric layer 82 causes it and the brass disk 80 to flex alternately convexly and concavely, thus launching a sound wave. Alternatively, if an externally generated sound wave flexes the piezoelectric assembly, a voltage signal is generated between the two contacts in proportion to the intensity of the sound wave. The piezoelectric transducer 50 is mounted to the annular ridge 76 at a vibrational node of transducer 50, at a diameter at which no vibration occurs. This mounting method causes the least mechanical suppression of vibration and thus provides for the highest efficiency of the transducer.
The cavity 72 together with the sound port 86 to the surrounding environment form a Helmholtz resonator. The dimensions of the cavity 72 and the sound port 86 determine the frequency of the resonator, here around 6500 Hz. The Helmholtz resonator is a harmonic oscillator and can be analogized to a weight attached to a spring, both of which can be described by the same equations. The air in the inner cavity 72 compresses and expands analogously to the motion of a spring, and the air in the sound port 86 is pushed back and forth and is analogous to the weight. Note that the Helmholtz resonator functions only when the cube root of the volume of the cavity 72, the square root of the area of the sound port 86 at the interface to the cavity 72 and the effective length of the sound port 86 are all significantly less than the wavelength of the sound at the resonant frequency.
Prior-art Helmholtz resonators used in conjunction with piezoelectric transducers use a single circular port above the cavity 72. Such a structure has two disadvantages for a lost item finder. If the single sound port for the Helmholtz resonator is lying on a surface face down, or for example, sandwiched between two pillows on a sofa, the resonant characteristics of the resonator will be adversely altered and the emitted sound will be significantly blocked. Further, the intensity of the sound directly in front of the sound hole of the conventional Helmholtz resonator is very loud, and it can even be painful to someone who might place it directly up to his ear. To overcome these problems, the resonant cavity 72 is preferably covered with a cap 26 spaced from the case half 70 by three unillustrated standoffs so as to form a sound port that is an annular channel 86 of predetermined height and length, where the height of the cap 26 and dimensions of the cavity 72 are chosen to form a resonant system that resonates at 6500 Hz.
I have derived an approximate formula for the resonant frequency of the cavity
where c is the velocity of sound (3.44�104 cm/s at 24� C.), d is the diameter of the cavity 72, g is the gap between the outer face of the cavity 72 and the cap 26, and h is the height of the cavity 72. Exemplary values are d=1.27 cm, g=0.102 cm, and h=0.381 cm, which imply that the resonant frequency f0 is 6488 Hz.
With the structure for the Helmholtz resonator of FIGS. 4 and 5, the sound is much less likely to be blocked because it is emitted in a 360 degree pattern parallel to the face of the device. Further, the maximum sound intensity immediately in front of the improved resonator is significantly less than that immediately in front of a comparably efficient prior-art resonator. In one experiment the prior-art device and the improved device were found to generate the same intensity sound at a distance of 5 centimeters and beyond. At a distance of 0.5 centimeters, however, the improved device generated a sound pressure level that was 15 dB quieter than the prior-art device. Furthermore, the cap 26 protects the piezoelectric element 50 from being damaged by foreign objects.
The finding system of the invention can be programmed to operate in a number of different modes. The programming may be accomplished by coding the necessary instructions in the assembly language of the microprocessor and impressing those instructions in machine code form into the non-volatile memory of the microprocessor 40.
One set of operating procedures will now be described based upon a coded sequence of tones schematically illustrated in FIG. 6. The tone sequence is used to communicate a search signal from the available locator to a lost locator. Each audio tone is at a fixed frequency and of finite duration. A single such tone sequence can in many circumstances be sufficient for finding the lost locator, but it is anticipated that the user will repetitively activate the locator's transmitter for yet further such sequences. Once the lost locator has verified that the coded sequence has been received, it emits both an acoustic and an optical signal acting as beacons to the user attempting to find the lost locator. A baseline frequency f0 is assumed to exist in the 5500 to 7500 Hz range. Audio signals in this range can be efficiently generated and received within a small case. Its precise value may depend upon environmental and aging effects of the transducer and its electronic controls. An inexpensive RC clock internal to the microprocessor 40 is accurate to no more than �10% so timing between multiple locators must accommodate such variations. Further, a procedure is available to change the baseline frequency to one found to be most sensitive in actual use. The lost locator however, should be able to detect the coded tone sequence regardless of the baseline frequency f0 as long as it is within the permitted range.
The tone sequence includes a first tone 90 at the baseline frequency f0 enduring for 170 ms followed by a first quiet period 92 of 250 ms. A second tone 94 is emitted at a frequency that is 250 Hz below the baseline frequency f0 for a period of 120 ms followed by a second 250 ms quiet period 96. A third tone 98 is emitted at a frequency 50 Hz below the baseline frequency f0 for a period of 120 ms followed by a third 250 ms quiet period 100. A fourth and final tone 102 is emitted at a frequency 250 Hz below the baseline frequency f0 for a period of 120 ms. A long quiet period 104 follows the tone sequence until another such tone sequence is transmitted as a further search signal.
This coded sequence is advantageous when operating in a noisy environment including, for example, music, conversation, or other combinations of noise. In such an environment, it is possible that almost any frequency is likely to be detected at some time. The precise frequency shifts, however, are unlikely to be duplicated by background noise. The frequency changes and the relatively long quiet periods also overcome interference resulting from the generated tones echoing for tenths of seconds or more in some rooms.
To further improve the reliability of the locator by accommodating situations where the tone sequence is duplicated by environmental noise, one feature requires that a quiet period be observed at the end of the tone sequence. The requirement that the tone sequence be followed by a quiet period all but eliminates the possibility of false alarms, but it also creates a problem. In noisy environments a locator will not respond to the tone sequence generated by another locator because the quiet period will not be observed. To resolve this problem, the requirement that a quiet period be observed may be temporarily suspended for approximately ten seconds when the tone sequence is recognized but the quiet period is not observed. Temporally removing the required observation of a quiet period does not create a problem, however, because it is very unlikely that any noise source will produce two valid sequences of the search signal in a ten second period. Thus, in a noisy environment the locator will not respond on the first try but it will respond on the second try and each try thereafter as long as each try is within ten seconds of the previous try. Having to press the signaling button more than once is not a problem because this is the normal mode of operation for a person anxious to retrieve a lost item.
The microprocessor 40 may be programmed to perform many different functions. However, an advantageous set of functions is described with respect to the following diagrams.
During periods in which the finding system is not being used, the microprocessor 40 remains in a SLEEP mode consuming very little power and doing little more than awaiting a Wake Up 110, a form of processor reset, as illustrated in the flow diagram of FIG. 7. Wake Up 110 occurs when, during the SLEEP mode, either the microprocessor's IN-1 or IN-2 input changes state in either direction, that is, either the button 22 is pressed or released, or a further 128 pulses have been detected by the divide circuit 60. Signaling data on the IN-3 input does not cause a Wake Up. The microprocessor 40 is also reset when the battery is first installed or replaced. Depending on whether the reset was the result of installing the battery or waking up as the result of an input changing state, different initializations are made to put the microprocessor 40 and other circuitry in the correct state. A test 112 is then made for whether the button 22 is pressed by determining if the IN-1 input is low. If it is, processing is diverted to a BUTTON PRESSED routine 114 to be described later with respect to FIG. 9. If it is not pressed, the time T is measured in step 116 for the receipt of five input pulses on the IN-3 input. If test 118 determines that the time T is not between 650 and 950 μs, that is, an average frequency of between 5300 and 7700 Hz, then processing returns to the SLEEP mode 120.
If the time T is within specified limits, an initial counting step 130 measures the number of pulses arriving on the third input IN-3 over a 10 ms period. This 10 ms count occurs many times during the receiving algorithm. It is easily implemented knowing how long it takes to execute each instruction in the microprocessor 40. A small loop is executed a fixed number of times while the number of high-low transitions on the third input IN-3 is counted. For a 5500 to 7500 Hz audio signal, the number of counts would be between 55 and 75. While counting the pulses, the time between successive pulses is also measured. At low levels, noise (either acoustic or electronic) can cause a pulse to be missed. Therefore, if the spacing between pulses is between 260 and 350 μs, twice the expected spacing, the algorithm assumes that a pulse has been missed and it adds a count. If during a 10 ms period the number of missed pulses exceeds seven, the process does not continue to add counts; the pulse train is either too corrupted to be accurately corrected or it is being generated from sounds other than the signaling tone.
Test 132 determines if an average count has already been determined. If it has not yet been determined, in step 134, the average count is determined from the first ten 10 ms counts of step 130. The averaging may advantageously discard the highest three and lowest three counts and average the remaining four counts. If at any time during the averaging process the highest and lowest count differ by more than two counts, a decision is made in step 136, and the processing returns to the SLEEP mode. If a decision to start over is not made, the process returns to step 130 to determine the number of pulses that arrive during the next 10 ms counting period.
If test 132 shows that the average count has been determined, processing skip to step 138. At this point, the first tone has been determined to have been identified, and the value of the average count is determined to correspond to the baseline frequency being used by the sender. Also, a time of so identifying the first tone is saved. Then, test 138 determines if the flag has already been set indicating the identification of the fourth tone. If the fourth tone has been identified so that the full tone sequence has been received, execution transfers to transfer point A in FIG. 8, the start of a routine that is concerned with features for dealing with background noise. If the fourth tone has not been identified, a test 142 determines if more than 500 ms has elapsed since the identification of the previous tone, specifically the first, second, or third tone. If such a long period has elapsed, then the anticipated tone is determined to have not been received and the process is returned to the SLEEP mode 120.
If less than 500 ms has elapsed, then test 144 determines if the second tone has already been identified. If it has not, then step 146 attempts to identify the second tone. The second tone is a tone about 250 Hz lower than the first tone, Therefore, its 10 ms counts must be two or three counts less than the baseline count. The identification of the second tone is successful when four of five sequential 10 ms counts meet the criteria, whereupon a flag is set for the identification of the second tone and the time is saved for when this occurred. Whether or not the second tone has been identified in step 146, processing returns to the 10 ms count entry point 148 leading to the initial counting step 130 to determine the number of pulses that arrive during the next 10 ms counting period.
If test 144 determines that the second tone has already been identified, test 150 determines whether the third tone has been identified. If the third tone has not been identified, step 152 attempts to identify the third tone. The third tone is a tone about 50 Hz lower than the first tone. Therefore, its 10 ms counts must be zero or one counts less than the baseline count. The identification of the third tone is successful when four of five sequential 10 ms counts meet the criteria, whereupon a flag is set for the identification of the third tone and the time is saved for when this occurred. Whether or not the third tone has been identified in step 152, processing returns to the initial counting step 130 to determine the number of pulse that arrive during the next 10 ms counting period.
If test 150 determines that the third tone has already been identified, then step 154 attempts to identify the fourth tone following the same criteria as for the second tone identification 146. When the fourth tone is identified a flag is set for its identification and the time is saved for when this occurred. Whether or not the fourth tone has been identified in step 154, processing returns to the initial counting step 130 to determine the number of pulses that arrive during the next 10 ms counting period.
With reference to FIG. 8, transfer point A from FIG. 7 is followed by a test 160 for determining whether a background noise timer remains set, that is, has not expired by being decremented to zero.
If the test 160 determines that the background noise timer is no longer set, a test 162 determines whether a period of 1500 milliseconds has elapsed since the fourth tone has been identified. If 1500 milliseconds have not elapsed, step 164 attempts to identify a quiet period. A quiet period is identified when four out of five sequential 10 ms counts have count values of less than 25. Test 166 determines if a quiet period has been successfully identified. If it has not been, processing returns to the initial counting step 130 to determined the number of pulses that arrive during the next 10 ms counting period. Since the average count has already been determined and the fourth tone has already been identified, test 132 followed by test 138 of FIG. 7 will return to transfer point A with the required 10 ms count.
If test 166 determines that the quiet period has been identified, the search for the signaling sequence has been successfully completed, and step 172 performs the beacon signaling, which preferably includes sounding the audible buzzer implemented with the piezoelectric transducer and flashing the LED for a predetermined length of time of, for example, eight seconds. The audible beacon signal is generated by setting the third microprocessor output OUT-3 to activate the tri-state buffer 48 and outputting a square wave on the second output OUT-2 at the desired audio frequency. The visible beacon signal is generated by outputting a rectangular pulsed signal on the first output OUT-1 at a frequency and duty cycle selected for the flashing LED signal. However, only one of the visible and audio signals are required for the beacon signaling. The frequency of the audio signal may be selected to be most audible to the user but should be within the range that can be handled by the piezoelectric transducer and its associated resonant cavity. After the beacon signaling of step 172, the SLEEP mode 120 is entered.
Returning now to test 160, if the test determines that a background noise time remains set, it is reset back to ten seconds at step 154. Resetting the time back to ten seconds allows sequential search signals, spaced at intervals of less than ten seconds, to be recognized in the absence of a quiet period at the end of each. Thereby, this and subsequent quick button pushes on an available locator will cause the beacon signal from a lost locator to be generated.
If test 162 determines that more than 1500 milliseconds have elapsed since the identification of the fourth tone, the conclusion is that no quiet period has been observed in a reasonable time after the tone sequence has been identified and that the environment is very noisy so that no quiet period is likely to be observed. However, rather than assume that a valid tone sequence has nonetheless been received, the algorithm requires that the user again press the button within a 10 second period. The requirement that the user send out a second set of search tones further reduces the possibility of false recognition. To accomplish this, step 168 sets the background noise timer to 10 seconds and execution returns to the sleep mode 120 awaiting receipt of another tone sequence. Assuming the user does reactivate the identification procedure of FIG. 7 within ten seconds, when processing returns to the noise analysis of FIG. 8, the noise timer will again be reset to 10 seconds.
The process described above with respect to FIGS. 7 and 8 primarily concerns the operation of the lost locator that is being sought by the available locator. The description now turns to the operation of the available locator, the sole activation of which in most circumstances is the pushing of the button by the user. The available locator generates the search signal, but other types of operations are possible, as will be described.
As illustrated in FIG. 9, the process is initiated by the Button Pressed 114 corresponding to the user pressing the button 22 and closing the switch 62 of FIG. 3 to thereby pull the input IN-1 low. This point may have been reached following the Wake Up 110 of FIG. 7 from the SLEEP mode or may be accomplished by a the button 22 being pressed with the microprocessor being in its active mode. Test 182 determines if a Single Press timer remains set and has not expired. The Single Press timer allows a circumvention of the usual system requirement that the button be pressed at least twice within one second to initiate the transmitting of the search signaling tone sequence. The requirement that the button be pressed twice prevents spurious signaling when the locator button is accidentally pushed, for example, as it is jostled in a pocket or purse. If the Single Press timer remains set, indicating that the button was double pressed within the preceding 15 seconds, step 184 generates the audio tone sequence represented in FIG. 6 that constitutes the search signal.
On the other hand, if the Single Press timer was never set or has expired, test 186 determines if the button has been doubled pressed, that is, pressed a second time within one second after the release of the first button press. If it was not again pressed in this short time, test 187 determines if the button is still held down from the first press. If the button is no longer pressed, operation is returned to the SLEEP mode 120. If the button continues to be pressed, step 188 turns on the LED allowing it to be used as a search light to view objects in the dark such as keyholes and the like. Thus, if the user instead of doubling clicking the button to transmit a search signal, instead presses the button down and holds it down, the LED acts as a flashlight for the duration of the button being held down. In step 189, when the button is released, the LED is turned off, and operation is returned to the SLEEP mode 120.
Returning now to test 186, if the button was pressed twice within one second, step 184 generates the audio tone sequence of the search signal. In step 190, the Single Press time is set to 15 seconds. Step 192 is a wait state of up to 0.5 seconds if the button remains pressed. After the 0.5 second wait, test 194 determines if the button continues to be pressed. If it is not pressed, operation returns to the SLEEP mode 120, during which a further pressing of the button will return operation to the Button Pressed point 114 at the beginning of FIG. 9.
If the button continues to be pressed in test 194, step 196 generates a short double beep tone to warn the user that he needs to make a decision during the next two seconds. Step 198 waits up to 2 seconds while the button continues to be pressed. Test 200, illustrated in FIG. 10, then determines if the button continues to be pressed. If the user has released the button so it is not pressed, the locator is placed in a 90 second wait state 204 waiting for the button to again be pressed. During this time, the associated locator is inactive even to the receipt of search signals. This 90 second wait is useful in inactivating a third locator while a first locator is searching for a second locator. Responses from the third locator would result in two beacon signals from the second and third locator which would frustrate the search for the lost second locator. If at any time during the 90 seconds the button is pressed, test 206 determines the current state. If it is pressed, operation transfers to a Generate Tones point 208 just before the step 184 for generating the audio tone sequence of the search signal. This allows the user to use the unit before 90 seconds has elapsed. During those 90 seconds, it would be very disconcerting for the user to press the button and hear no response. The 90 second wait should be sufficient for the first locator to find the second locator. If the button, on the other hand, is not pressed during the 90 second deactivation period, operation returns to the SLEEP state 120.
If the user has continued to press the button after the two second wait 198, the test 200 is positive, and step 210 generates a short triple beep tone sequence. The short triple beep notifies the user that he needs to make a decision during the next two seconds in regards to a frequency calibration procedure for setting the baseline audio frequency f0. Step 212 waits up to 2 seconds while the button continues to be pressed. Test 214 then determines if the button continues to be pressed. If it is pressed, step 216 sets the baseline audio frequency to 6500 Hz, the middle of the resonant frequency range of the piezoelectric transducer and its associated resonant cavity. Then, step 218 generates a short quadruple beep tone to indicate to the user that the baseline frequency has been reset to the default value of 6500 Hz. A wait release state 220 is continued until the button is released, and thereafter operation returns to the SLEEP mode 120.
If, on the other hand, the user released the button during the two second wait 212, test 214 is negative resulting in step 226 setting the baseline frequency to an interim value of 5500 Hz. The tone at the interim baseline frequency is generated for up to 10 seconds or until the button is pressed. Test 230 determines whether the button is pressed. If it is not, operation returns to the SLEEP mode 120, and the interim baseline frequency is ignored and the old value of the baseline frequency is retained.
If test 230 shows that the button is pressed, another wait state 232 is entered, following the cessation of the audio tone at the interim baseline frequency, where it will wait up to seconds while the button continues to be pressed. During this period, the user must decide if he is satisfied with the interim baseline frequency or wishes to cycle through the remaining available frequencies. Test 234 determines if the button continues to be pressed. It if continues to be pressed after two seconds, step 236 converts the interim baseline frequency to the permanent one. Operation transfers to the quadruple beep step 218 awaiting release of the button and transfer to the SLEEP mode 120.
If, however, the user released the button during the 2 second wait period 232, test 234 is negative and step 238 increments the interim baseline frequency by 125 Hz. Test 240 determines whether the incremented value is greater than the maximum permitted value of 7500 Hz. If it is not above 7500 Hz, operation returns to step 228 for generating the audio tone at the newly incremented value of the interim baseline frequency. If the increment value is above 7500 Hz, operation returns to the frequency initialization step 226, which resets the interim baseline frequency to 5500 Hz and continues the frequency setting sequence.
The baseline frequency f0 may be reset by this procedure to increase the sensitivity of the lost locator to the search signal. Note that if the piezoelectric transducer and its associated resonant cavity were guaranteed to exhibit peak performance around 6500 Hz and the clocks in the microprocessors where guaranteed to all run at close to the same frequency, the described calibration procedure would be unnecessary. In actuality, both the piezoelectric transducer and its associated resonant cavity as well as the clock in the microprocessor have tolerances no more precise than �10%. When using the default baseline frequency of 6500 Hz, almost all units will work, however, the operating range in some instances can be improved by changing the frequency. Note that even the 6500 Hz default frequency will vary from locator to locator because the clocks in the microprocessors that control the tone generation will vary in frequency.
It is understood that the above described algorithm does not include many of the details of initialization, synchronization, and timing. However, these are standard issues easily addressed by a programmer of ordinary skill.
As described, any one of thousands of locators manufactured according to the described embodiment can be used in conjunction with any other of the many locators. Although this feature simplifies the manufacture, inventory, and distribution of the locators, an interference problem may arise if the locating system is widely used by many different parties in a close space. For example, multiple users using the system to locate coats in a restaurant coat room. The described system does not differentiate between different users. However, it is possible to set up more complex search signaling algorithms. For example, a longer sequence of tones may be used in which the frequency changes are programmed differently between a significant number of users. This could be accomplished by an 8-bit toggle switch embedded in each locator and changeable by the user to allow 256 different tone sequences. A means could also be provided to program different tone sequence codes into erasable non-volatile memory embedded in each locator.
The use of acoustic search signaling is advantageous in not needing to meet any government standards for electromagnetic emission. Such acoustic signaling can thus be advantageously applied to other types of finding systems in which the search unit and the beaconing unit have different designs with no ability to perform the other function.
The paired object locating system of the invention is not limited to using acoustic energy to signal a lost locator. Another approach has the paired locators using radio frequency (RF) signaling techniques such as are commonly used in garage door openers and automobile door remotes. During manufacture or in the field, the coding information for use by both the transmitter and receiver would be encoded into two or more matched locators so that an encoded RF signal emitted by one of them is recognized by any other of them. For example, as illustrated schematically in FIG. 10, an RF transceiver 250 is connected to an antenna 252 for both transmission and reception of a search signal. A controller 254 programmed with algorithms similar to those described for the acoustic finding system both controls the RF transceiver 250 and receives signals from it. Manual activation of the button controlled switch 62 connected to the controller 254 causes it to instruct the RF transceiver 252 to transmit an RF signal coded according to an identification code provided by the controller 254. When such an RF search signal is received by an associated locator, its RF transceiver 250 transfers the coded message to its controller 254, which checks whether the identification code is a match. If it is not, the search signal is ignored. If it is the same code, the controller 254 broadcasts beacon signals on the LED 20 and the audio transducer 50. Of course, the RF identification codes may be more complex. Two different codes may be paired between two locators, or one locator may be selectively activated to find only one of several other locators.
It is of course appreciated that the locators can be incorporated as integral parts into other similarly sized items. For example, many automobiles are now sold with remote entry systems having a pocket remote key fob for locking and unlocking the car doors and the like, and usually two such remotes are supplied with the car. The locators of the invention can be incorporated into such remotes. Some car keys are intelligent in that they have embedded RF identification chips and RF transmitters for added security in starting the car. Again, the locator of the invention may be incorporated into the already enlarged head of the intelligent key. Also, the car key code may be used as the search code for the finding system.
The invention as described combines simple, compact, and inexpensive structure and circuitry with many programmable functions. Since the features are implemented in large part in software, the system is flexible and can accommodate additional functions. The described algorithm is illustrative only, and the same or similar functions can be programmed in different manners.
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|Jun 20, 2014
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|Apr 13, 2006
|Bernal-Silva Richard A
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|Oct 21, 2005
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|Mc Call Clark E
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|Aug 7, 2008
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|U.S. Classification
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|International Classification
|Cooperative Classification
|European Classification
|Jul 28, 2006
|Fee payment
Year of fee payment: 4
|Dec 3, 2010
|Fee payment
Year of fee payment: 8
|Sep 21, 2014
|Fee payment
Year of fee payment: 12


text:
William Steuart Trench and His Management of the Digby Estate, King's County, 1857-71
By Mary Delaney
This book establishes what the true 'realities' were on the Digby estate in King's County from 1857 to 1871, under the management of William Steuart Trench. Trench was a professional land agent who had previously worked on the Bath Estate in Co. Monaghan and the Lansdowne Estate in Co. Kerry. The barony of Geashill experienced a golden age of prosperity. There were vast improvements in both the architecture of the village and in the topography of the landscape during the Trench years. Such improvements gained both national and, indeed, international recognition for Lord Digby and earned Trench the legacy of an improver who was well ahead of his time. However, not all members of the community shared in this prosperity and while the physical legacy of Trench lives on, it is overshadowed by the realities of an agent who broke leases, levelled people's homes, banished the poor, and, in so doing, was ruthless in his management of Lord Digby's estate. Trench's realities were therefore not the only realities experienced by the people of Geashill. (Series: Maynooth Studies In Local History - Number 101)
56 pages
Publication Date: 9/13/2012
Format: Paper

subset: commoncrawl


text: Elio de Angelis was born on 26th March, 1958 in Rome. He hailed from a wealthy family and since a young age cut his teeth on karts. In 1977, he competed in the Italian F3 championship, and finished second in his fourth race. He eventually went on to win the title at his first attempt. The following year he raced in the F2 championship and though his performance was quite disappointing, he managed to make a mark and was offered to test for the Shadow F1 team. Lotus signed him up in 1980 and at the age of 21, he finished second at Interlagos and became one of the youngest Grand Prix winners of all time.Angelis went on to spend six seasons for Lotus. His first victory came in the Austrian Grand Prix in 1982 though the year and the one that followed brought in quite disappointing results. 1984 turned out to be his best season ever. He not only managed four podium finishes and but also was consistent enough to finish third in the driver's rankings despite not winning even a single race. Then followed his second win at San Marino in 1985 and he finished fifth in the rankings. But the arrival of Ayrton Senna and his political prowess at Lotus in the beginning of 1986 forced Angelis to quit and move to Brabham in place of Nelson Piquet.During a testing session in France on one of the fastest sections of the track, Angelis was driving a BT55, a Brabham car with the BMW engine. It was a machine that looked fantastic but was a complete failure. Soon Angelis' car lost its rear wing and smashed into a fence, turned upside down and caught fire. He was rescued after almost 30 minutes due to lack of marshals and the delayed arrival of the rescuing helicopter. He died 29 hours later in hospital as a result of asphyxiation due to inhaled smoke.Elio de Angelis had a cool, laidback personality that masked a drive for competition and a genuine love for the sport. His death left a huge void in the racing world. Neither was he one of the most talented drivers nor did he belong to the category of serious championship material. But the sophistication and charm he brought to the sport was rare among his contemporaries and set him a class apart.-Saahil Desai


text:
Flooring Installation, Sales, and Service
The Flooring Pro Guys
While it can appear to be very time consuming to find dependable flooring contractors in Columbus, OH, it just doesn't have to be. You shouldn't have to use your time to find out which contractors are reliable and that are not. When it involves the top-notch and most popular flooring contractors, the Flooring Pro Guys are the very best that Columbus has to offer. When you are searching for potential contractors to hire, we have some techniques and tricks to use to make your search easier.
Hundreds of options and samples to choose from!
Value Vs. Price for a Floor Installation
When you're considering working with a flooring contractor, you have to keep in mind that it's a difficult process to find the harmony between pricing and value. Hiring the cheapest contractor will typically end up costing you more in the long haul because they'll use poor quality materials and do a poor job. If you need to make sure that your project only has to be done once, you might not really need to hire the cheapest contractor you can find. Take some time to go to the internet and do some research on the variety of flooring types and their quality before you choose one.
A flooring contractor who quotes you a price substantially lower than the competition might not be the most qualified person for the job. There's a reasonably high rate of turnover in the service provider business, and a group of local contractors are certainly in the "here today and gone tomorrow" category. It's not unusual for flooring contractors to go out of business and leave their customers with worthless warranties. The warranty coverage needs to shown to you in visual form.
Local References
It can only be beneficial to request three local area references from your contractor. The references of your chosen contractor should be near flawless. We always can provide you with info on customers who've already experienced our expertise and quality work we provide. The Flooring Pro Guys can put you in contact with any number of satisfied customers who will attest to the quality results we've delivered.
Contact the references provided by the flooring contractors and inquire about the way their property was handled by the crew. Ask how they cleaned up the mess upon completion of the flooring job. Also ask if their home was returned to its original condition when the job was completed. Any contractor who doesn't care about your property isn't who you need for your flooring job.
A Professional Flooring Contractor
Never miss out on seeing their liability insurance policy before you decide to hire. Any contractor that's not a liability will have sufficient insurance policies in place for flooring projects. Doing work with an uninsured contractor is something you should never do. Insured contractors pay close attention to details to avoid lawsuits which can lead to an increase in their insurance premium.
Vehicles of experienced contractors will have proper signage advertising their services. A fraudulent contractor will be in a position to rent or borrow a vehicle easily. Always find out if the phone number you'll be calling is a local one. Give the company a call via the phone number displayed on their vehicle to check if they answer professionally.
A Quality Flooring Installation
An actual professional will supply you with a step-by-step plan on how they'll and can control any type of mess, if you make the decision to occupy the property throughout the project. In the event that you do not plan on occupying the property while the flooring project is occurring, your service provider should still be able to construct a pre-project plan and present it to you. When you could expect the project to be finished, the schedule and the details surrounding the project need to be shown to you. The Flooring Pro Guys can make sure that you're properly taken care of during the duration of your project.
Get the full list of processes involved with the project from beginning to its end when working with a flooring contractor. Contractors pick and choose strategies that work best for them, either completing one room or one house at a time. Any and all flooring jobs will create a mess, so make sure to check how the crew disposes of trash. Also make sure there will be a thorough cleanup when the job is completed.
It's A Messy Job!
Query how the flooring contractor will avert a potential mess during flooring. It's common practice among flooring contractors to drape each room with heavy plastic sheeting. Plastic sheets are overlapped to create a barrier that doesn't let dust particles escape. 'Men Working. ' tape is used to wrap the room in red, warning others not to disturb the work in progress.
Unfinished flooring areas should have heavy plastic draping to prevent children from entering the room. Ask if the draping is covered in the quoted price. Children that are not monitored can easily come upon a nail or two. Potential injuries can be avoided by contractors who carry themselves in a professional manner. No reputable flooring contractor will risk injury to any member of your household, especially children.
A Professional Flooring Installation From A Trusted Flooring Contractor
Every professional flooring contractor with experience in flooring service should know his product lines from memory. He should present a professional presentation of the merchandise lines that are available upon request. A real contractor should know the merits and demerits of each and every flooring product he offers, and he should be in a position to quote the various options and their respective prices from memory. A contractor who may have to look up product features and prices probably hasn't been in the business for very long.
Your exact job requirements must be written into the legal agreement just as how they were presented to the service provider. Money and stress can be saved over time if the requirements of the legal agreement are stated and adhered to. Until you have presented all of your questions and concerns about the job to your local contractor, do not sign anything. Legal terms tend to be put into contracts to confuse the person signing the papers. Make sure to have an attoney verify the contents of the legal agreement.
Sometimes, no matter how much you love the color and texture of the stain you picked out for your hardwood floor, it just doesn't look right after the very first coat has been applied. Extra charges usually are involved for wasted material and time, so selecting durable stain instead of low quality ones is vital. A customer should always receive the highest level of expertise from their chosen contractor. What the Flooring Pro Guys want is for you to be tickled, happy, and delighted about the service they've provided.
Contact Us:
The Flooring Pro Guys
Columbus, OH
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text:
The 38-year-old woman is believed to have been returning from a shopping trip when she casually strolled across railway lines carrying two bags.
Minutes later a high-speed train capable of 125mph was forced to slam on its brakes to avoid hitting her.
Amazingly, the driver then stepped down from the cabin and helped the woman into the cab before driving her to nearby Bristol Parkway Station. The bizarre scenes were captured by trainspotter John Hobbs as he waited on a bridge to photograph a special service due from Birmingham.
Mr Hobbs, 61, a school caretaker from Westbury-on-Trym, Bristol, said the woman appeared to be very "laid back" despite the danger. He said: "I heard some shouting from the tracks and saw three guys wearing orange jackets shouting at this woman to get off the line. She had a few bags of shopping with her so I thought I'd take a few pictures because it was a very unusual situation. She was totally oblivious to the danger. I thought she must have been suffering from some sort of illness but when I spoke to the transport police they said she was fine."
A British Transport Police spokesman confirmed they are investigating the incident and revealed that the woman involved was not in a disturbed state.
- More about:
- Bristol (england)
- Railroad Traffic
- Railway


text:
NikiAlex Zander
Your Plan - Poem by NikiAlex Zander
Your Love runs through My Veins.
You were My life. Why did I want change?
You carried Me this far and I bailed.
Your Word is Truth, I'm the one who failed.
Your Plan was not to fail,
My plan was planned all wrong.
Will this be, My 'Death Song'?
Now I have Never felt so Sad.
Now I have Never been so Mad.
When I'm with You, I'm eternally glad.
Will We have a 'Happy Song'?
Will My life go from right to wrong?
Will this be My happy time?
I do believe in You, You are Divine.
Say a prayer, ask to be freed from Sin,
Knock on My door, ask to come in
And I will let you,
Come back in.
Topic(s) of this poem: made in usa
Poet's Notes about The Poem
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Edgar Allan Poe


text:
Cesc Fabregas - Chelsea can win the title this season
Chelsea midfielder Cesc Fabregas is convinced his side can retain the Premier League title, despite their disastrous start to the season.
Chelsea head into this weekend's Premier League action just four point clear of the relegation zone and 10 points behind leaders Manchester City, but Fabregas is convinced they can get back into the title race.
"I still believe we can win the league," he told The Sun. "It's not going to be easy but a 10-point gap at this stage of the season is not impossible.
"Last season we took 22 points from our first eight games but this time every team has lost at least one.
"It is a very strange situation for Chelsea to be at the wrong end of the table. And, for most of us at the club, it is the first time we have ever been down there.
"Now we know how it feels and we all hate it. At Chelsea, we always want to be at the top of the Premier League, fighting to win the Champions League, competing for every trophy.
"So it's clear this time we are doing things wrong and our performances have not been at the level required at this club. We have to change that, starting this weekend against Aston Villa."
Fabregas suggested the unpredictability of the Premier League gives Chelsea their best chance to mount a comeback after losing four times in their first eight matches.
"Manchester City lost to West Ham and Tottenham when no one expected it, Manchester United and Arsenal have also dropped points," stated Fabregas.
"No one at Chelsea is happy with our current position but I would prefer to be here now than at the end of the season.
"It's not how we start the campaign, it's where we finish it. There is still almost 80 per cent of the season to go so we have more than enough time to recover. But we need to start that recovery this weekend."
"We are dealing with our problems on the training ground as a group. We must work harder, plan better and compete better than we have.
"The 25 players, the manager and the coaching staff will work together to sort it. No one else will do us any favours."
Fabregas also offered his full backing to boss Jose Mourinho, who is now one of the favourites to be the next Premier League manager to face the sack.
"Jose is the best manager in the history of this club and the best manager we can possibly have. There is no one better to turn this around," he added.
"He always makes the best decisions and I'm sure he will get the best out of us again."


text:
The Marvel Cinematic Universe "Phase Two" collection arrives at Amazon.com on December 8th. We have reported in the past on its extensive special features, and Marvel has just released some new exclusive artwork. Every DVD in the collection will have a custom disc sleeve featuring new illustration by artist Matt Ferguson.
You can check out the high res images below!


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SHEPHERDSVILLE - One of the top in-season girls' high school golf tournaments in the state will take place on Saturday at Heritage Hill Golf Course.
HEBRON ESTATES - The newly revived Bullitt East-North Bullitt soccer rivalry continued on Saturday as the teams battled through a hot afternoon before Bullitt East secured a 1-0 victory in the Bullitt Cup.
LEBANON JUNCTION - China painting has been a highly regarded art form for thousands of years, dating back to prehistory.
LEBANON JUNCTION - After serving a brief stint at the helm of the Lebanon Junction Police Department, former Bullitt County Sheriffs Deputy Danny Thompson recently called it quits, citing health issues as the reason for his resignation.
SHEPHERDSVILLE - When parties gather on Thursday to litigate the issue of a smoking ban imposed by the Bullitt County Board of Health, only one concern will be addressed.
SHEPHERDSVILLE - A new member will soon take a seat on the Shepherdsville City Council.
This week Paul Coyle takes a look at the recession's toll on government, both nationally and locally.
SHEPHERDSVILLE - Her goal is quite simple - to have a shelter where abused men, women and children can go for protection.
BARDSTOWN JUNCTION - Any hopes that a controversial rezoning request would be decided earlier than the planned Sept. 6 meeting of Bullitt Fiscal Court was quickly extinguished Tuesday.
SHEPHERDSVILLE - As part of the quest toward preparing students for life after high school, officials looked at some very poor numbers last year.
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The Pioneer News Online is your source for local news, sports, events and information in Bullitt County and Shepherdsville, KY, and the surrounding area.


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Administration of zoledronic acid enhances the effects of docetaxel on growth of prostate cancer in the bone environment
After development of hormone-refractory metastatic disease, prostate cancer is incurable. The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. In this study we have examined the effects of a combination of zoledronic acid (ZOL), a new-generation bisphosphonate, and docetaxel on LuCaP 23.1, a prostate cancer xenograft that stimulates the osteoblastic reaction when grown in the bone environment.
Intra-tibial injections of LuCaP 23.1 cells were used to generate tumors in the bone environment, and animals were treated with ZOL, docetaxel, or a combination of these. Effects on bone and tumor were evaluated by measurements of bone mineral density and histomorphometrical analysis.
ZOL decreased proliferation of LuCaP 23.1 in the bone environment, while docetaxel at a dose that effectively inhibited growth of subcutaneous tumors did not show any effects in the bone environment. The combination of the drugs significantly inhibited the growth of LuCaP 23.1 tumors in the bone.
In conclusion, the use of the osteolysis-inhibitory agent ZOL in combination with docetaxel inhibits growth of prostate tumors in bone and represents a potential treatment option.
Patients with advanced prostate cancer (CaP) suffer from the severe consequences of hormone-refractory disease and bone metastases. After development of metastatic hormone-refractory disease, CaP is incurable, with a median survival of 9 to 12 months. Given the near-certainty that processes associated with hormone-refractory CaP and bone metastasis contribute directly to morbidity (pain, bone fractures, bone marrow failure) of patients, treatment modalities that would eliminate the advanced disease, slow down progression, or improve the quality of life of patients with advanced CaP are of great interest. Hormonal therapy, radiotherapy, and chemotherapy do not cure hormone-refractory disease
Zoledronic acid (ZOL) is one of the most potent of the new-generation bisphosphonates (BPs), compounds that inhibit bone lysis and have been used in the treatment of bone diseases and bone metastastatic disease
Docetaxel, an inhibitor of tubulin depolymerization, has emerged as the most valuable chemotherapeutic treatment for advanced CaP. Phase II studies have shown decreased prostate specific antigen (PSA) levels and increased survival, with dosage amounts and regimens varying from 25–75 mg/m2 every 1 or 3 weeks
The recent history of chemotherapy has shown that with difficult disease targets, combinatorial therapy frequently offers the best chance of a cure. Therefore testing of combinations of BPs with other agents is of significant interest in the treatment of various cancers. Many of the initial studies of BPs in combination with chemotherapy were conducted on breast cancer or myeloma, where the bone lesions are highly osteolytic. Combinations of taxoids with BPs
In this study we used a combination of ZOL and docetaxel to evaluate changes in bone remodeling and tumor growth of an osteoblastic CaP xenograft, LuCaP 23.1.
All procedures were performed in compliance with the University of Washington Institutional Animal Care and Use Committee and NIH guidelines. LuCaP 23.1 is a PSA-producing human CaP xenograft
Intra-tibial tumors and docetaxel and zoledronic acid treatment
The right tibiae of forty male SCID mice (four-to-six-week-old, Fox Chase SCID mice, Charles River, Wilmington, MA) were injected with 2 × 105 LuCaP 23.1 cells as we have described previously
Bone histomorphometry
BHM analysis was performed on 6-μm longitudinal sections of calcified tibiae stained with Goldner stain in the middle of the tibia from five animals per group (Skeletech, Inc., Bothell, WA). The percentages of bone volume and tumor volume in the whole longitudinal section of tibiae (% BV/TV and % TuV/TV, respectively) were calculated. Detailed analysis of the trabecular bone, including determination of trabecular thickness in μm (Tb.Th.), trabecular number per mm (Tb.N.), trabecular separation in μm (Tb.Sp.), the ratio of osteoblast surface to bone surface as a percentage, the ratio of osteoclast number to bone surface as a percentage, osteoid surface to bone surface as a percentage (Os.S/BS) and osteoid thickness (Os.Th.), was performed in the area adjacent to the growth plate (0.525–1.225 mm below the growth plate, site of injection). Statistical analysis of the results was done using paired and unpaired Student's t tests as appropriate.
Effects of docetaxel on subcutaneous tumors
Six-to-eight-week-old male SCID mice were implanted with LuCaP 23.1 tumor fragments over the right scapular region. Tumor volume was measured twice weekly and calculated as L × H × W × 0.5236. After tumors reached 200 mm3 in size, animals were randomized into two groups. Group 1: animals received intra-peritoneal injections of PBS every two weeks; Group 2: animals received intra-peritoneal injections of 20 mg/kg docetaxel (Bristol-Myers Squibb, Princeton, NJ) every two weeks. Tumor growth was monitored twice weekly. Animals were sacrificed when the tumors reached ~1000 mm3 or when animals were becoming compromised.
LuCaP 23.1 causes significant new bone formation with a pronounced periosteal reaction. Radiographs of ZOL-treated tibiae show denser bone with a smaller perimeter. Importantly the tibiae treated with the combination of ZOL and docetaxel show dense bone and decreases in the periosteal reaction. Therefore the radiographs demonstrate a decrease in the overall extensive periosteal bone formation observed with the LuCaP 23.1 intra-tibial tumors by both ZOL alone and the combination of ZOL + docetaxel. Representative examples of the radiographic appearance of tibiae from control and treated animals are presented in Figure
Figure 1
A. Radiographs of treated and untreated LuCaP 23.1 bone tumors
A. Radiographs of treated and untreated LuCaP 23.1 bone tumors. Extensive new bone formation stimulated by LuCaP 23.1 is visible in the control tibiae. Although substantial bone formation is also visible with ZOL and ZOL + docetaxel, these tibiae exhibit decreased periosteal activity compared to the control and docetaxel-treated tibiae. B.-E. Histological appearance of treated and untreated LuCaP 23.1 bone tumors. Sections stained with Goldner reagent show marrow or tumored areas in pink and bone in green. The growth plate is marked with the letter G. The ZOL- (C) and ZOL + docetaxel-treated groups (E) exhibit substantial increases in bone volume and decreases in tumor volume compared to the control (B) and docetaxel-treated (D) groups. F. Bone mineral density (BMD) measurements at sacrifice. BMD was measured for the non-tumored and tumored legs of all four treatment groups. BMD was higher in tumored tibiae than in non-tumored tibiae, but there were no significant differences among the four treatment groups.
Effects of osteoblastic CaP xenograft LuCaP 23.1 and ZOL and docetaxel on bone were further evaluated by measuring BMD. BMD of all tumored tibiae exhibited increased BMD in comparison to the non-tumored tibia (196–240% increases, p < 0.0001 for all, Figure
We next performed a more detailed analysis of the effects of the treatments on bone, using bone histomorphometry. Groups receiving ZOL (2 and 4) exhibited 58% and 75% increases in bone %BV/TV over the control group (p = 0.0836 and p = 0.0164). These results are consistent with the histological appearance of the tibiae (Figures
Table 1
Results of histomorphometrical analysis of effects of the treatments on LuCaP 23.1 and bone
TB.TH. (μM)
TB.SP. (μM)
OS.TH. (μM)
23.09 ± 9.34
30.62 ± 5.75
94.89 ± 31.75
6.06 ± 1.41
76.87 ± 20.90
7.24 ± 1.82
4.57 ± 0.29
15.97 ± 5.08
1.91 ± 0.35
36.51 ± 7.86
17.68 ± 6.79a
145.7 ± 31.64
5.08 ± 0.53
52.29 ± 13.51
3.96 ± 1.87
5.27 ± 0.45
8.46 ± 1.42a
0.83 ± 0.46a
29.46 ± 8.56
28.29 ± 11.18
81.53 ± 20.45
5.61 ± 0.90
100.6 ± 24.88
6.73 ± 1.84
5.21 ± 0.36
14.17 ± 4.36
1.19 ± 0.61
40.38 ± 8.73a
11.13 ± 3.41a,b
118.5 ± 25.56
5.59 ± 0.51
61.48 ± 21.83
4.77 ± 1.01
4.98 ± 0.40
11.92 ± 5.90
0.77 ± 0.42a
Tumored tibiae were harvested after seven weeks of treatment and embedded in methacrylate. Analysis was performed on Goldner-stained longitudinal sections of tibiae (n = 5 per group).
Results are presented as a mean ± SD.
a p < 0.5
b p = 0.11 group 2
An important goal of our study was to determine the effects of ZOL and docetaxel and their combination on tumor growth. Tumor growth during the course of the treatments was monitored by PSA serum levels. Administration of ZOL and docetaxel alone did not decrease serum PSA levels in comparison to the control group (Figure
Figure 2
A. Effects of ZOL and docetaxel treatments on bone volume
A. Effects of ZOL and docetaxel treatments on bone volume. Bone volume as a percentage of the total volume was determined by bone histomorphometrical analysis. The ZOL + docetaxel treatment significantly increased bone volume compared to that of the control group (p = 0.0164, *). %BV/TV of the ZOL group was increased in comparison to the control group but the changes did not reach significance (p = 0.0839). B. Effects of ZOL and docetaxel treatments on serum PSA levels. Blood was drawn weekly from each treatment group, control (■), ZOL (●), Docetaxel (▼), or ZOL + docetaxel (○), and analyzed for PSA levels (ng/ml). The combination of ZOL + docetaxel decreased PSA levels significantly compared to those in the control animals. C. Effects of ZOL and docetaxel treatments on tumor volume. Tumor volume as a percentage of the total volume was determined by bone histomorphometrical analysis for the four treatment groups. The ZOL and ZOL + docetaxel treatments decreased tumor volume significantly (p = 0.027, 0.0002, respectively *) compared to that of the control group. The combination of ZOL and docetaxel resulted in decreased tumor volume in comparison to animals receiving ZOL alone; however, these results did not reach significance (p = 0.111).
We have also evaluated the effects of 20 mg/kg docetaxel on growth of subcutaneous LuCaP 23.1 tumors. This dose was effective in inhibiting growth of subcutaneous LuCaP 23.1 (Figure
Figure 3
Effects of docetaxel on growth of subcutaneous LuCaP 23.1
Effects of docetaxel on growth of subcutaneous LuCaP 23.1. LuCaP 23.1 fragments were implanted SC and animals were treated with 20 mg/kg docetaxel or placebo. Tumor volume was measured twice a week and blood was drawn weekly for determination of serum PSA levels. Mean ± SEM is plotted.A. Tumor volume: Docetaxel administration significantly decreased tumor volume compared to that of the control group. B. Serum PSA levels: Docetaxel decreased PSA levels significantly compared to those in the control animals.
CaP is an extremely heterogeneous disease, and to date treatment strategies with single agents have failed to cure advanced prostate cancer. New multimodality therapeutic combinations that target different pathways and produce pronounced and sustained clinical activity without severe toxicity are now considered the next frontier in treating advanced CaP. However, as expected, not all combinations will be superior to monotherapies;
ZOL has recently emerged as an effective treatment for inhibition of both normal and pathologic bone resorption, and this has had a major impact on the treatment of metastases to the bone. In advanced CaP, ZOL has been shown to significantly reduce bone pain and the incidence of skeletal complications
Although the main action of ZOL is inhibition of osteoclastic bone resorption
In the present study, administration of ZOL apparently had the effect of sensitizing the target cells to the effects of docetaxel. In fact in the presence of ZOL, the additional effect of docetaxel (~37% reduction in growth) was almost as great as that seen with ZOL compared with the control group (~42% reduction), although it should be noted that the comparison between ZOL and the ZOL/docetaxel combination failed to reach statistical significance because of modestly higher scatter within the ZOL-only group. Similar results were recently published by Kim
Our data show that the combination of ZOL and docetaxel is effective in inhibiting growth of osteoblastic metastases of prostate cancer. Because of the toxicity of chemotherapeutic agents such as docetaxel, it is important to insure that they are effective against disease as administered. Our data indicate that the single-agent effectiveness of docetaxel in the osteoblastic CaP environment may be limited, but ZOL may sensitize the target cells to the effects of docetaxel. These data support clinical evaluation of this combination in CaP patients.
CaP: prostate cancer, ZOL: zoledronic acid, DOC: docetaxel, BPs: bisphosphonates, SC: subcutaneously, BMD: bone mineral density, BHM: bone histomorphometry, BV/TV: bone volume in tissue volume, TuV/TV: tumor volume in tissue volume, Tb.Th.: trabecular thickness, Tb.N.: trabecular number, Tb.Sp.: trabecular separation, Ob.Pm./BPm.: osteoblast perimeter per bone perimeter, N.Oc./BS: osteoclast number per bone surface, Os.S/BS: osteoid surface per bone surface, Os.Th.: osteoid thickness
Competing interests
The author(s) declare that they have no competing interests. Studies were supported by a grant from Novartis Pharma AG, Basel, Switzerland.
Authors' contributions
KDB analyzed the results, and prepared the manuscript for submission;
LGB was involved in design of the studies and perform tissue culture;
RLV was involved in design of animal studies and discussion of the results;
EC was involved in design of animal studies, analyses of the data and their interpretation as well as writing the manuscript.
The authors would like to thank Dr. Michael Corey for editorial assistance and Ms. Janna Quinn for technical assistance. Zoledronic acid was kindly provided by Novartis Pharma AG, Basel, Switzerland, and Total PSA reagents by Abbot Laboratories. Studies were supported by a grant from Novartis Pharma AG.
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Inhibition of bone resorption by bisphosphonates: interactions between bisphosphonates, osteoclasts, and bone
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Sclerosis of lytic bone metastases after disodium aminohydroxypropylidene bisphosphonate (APD) in patients with breast carcinoma
Bisphosphonates promote apoptosis in murine osteoclasts in vitro and in vivo
Bisphosphonates induce apoptosis in human myeloma cell lines: a novel anti-tumour activity
Bisphosphonates induce apoptosis in human breast cancer cell lines
Bisphosphonates regulate cell growth and gene expression in the UMR 106-01 clonal rat osteosarcoma cell line
Early detection of bone metastases in a murine model using fluorescent human breast cancer cells: application to the use of the bisphosphonate zoledronic acid in the treatment of osteolytic lesions
Preclinical studies with zoledronic acid and other bisphosphonates: impact on the bone microenvironment
Bisphosphonate treatment inhibits the growth of prostate cancer cells.
Use of zoledronate to treat osteoblastic versus osteolytic lesions in a severe-combined-immunodeficient mouse model
Zoledronic acid exhibits inhibitory effects on osteoblastic and osteolytic metastases of prostate cancer
Bone microenvironment-related growth factors modulate differentially the anticancer actions of zoledronic acid and doxorubicin on PC-3 prostate cancer cells
Zoledronic acid induces apoptosis and inhibits adhesion to mineralized matrix in prostate cancer cells via inhibition of protein prenylation
Differential inhibition of invasion and proliferation by bisphosphonates: anti-metastatic potential of Zoledronic acid in prostate cancer
Comparison of Fc-osteoprotegerin and zoledronic acid activities suggests that zoledronic acid inhibits prostate cancer in bone by indirect mechanisms
Recommendations for zoledronic Acid treatment of patients with bone metastases
Safety and pain palliation of zoledronic acid in patients with breast cancer, prostate cancer, or multiple myeloma who previously received bisphosphonate therapy
Benefit of extended zoledronate therapy for patients with bone metastases from hormone-refractory prostate cancer
Re: Long-term efficacy of zoledronic acid for the prevention of skeletal complications in patients with metastatic hormone-refractory prostate cancer
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Understanding treatments for bone loss and bone metastases in patients with prostate cancer: a practical review and guide for the clinician
Re: A Randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma
Clinical benefit of zoledronic acid for the prevention of skeletal complications in advanced prostate cancer
The role of bisphosphonates in the treatment of prostate cancer
Skeletal complications of prostate cancer: pathophysiology and therapeutic potential of bisphosphonates
Weekly docetaxel and zoledronic acid every 4 weeks in hormone-refractory prostate cancer patients
A weekly schedule of docetaxel for metastatic hormone-refractory prostate cancer
Combination of docetaxel, estramustine phosphate, and zoledronic acid in androgen-independent metastatic prostate cancer: efficacy, safety, and clinical benefit assessment
A phase II trial of docetaxel and estramustine in patients with refractory metastatic breast carcinoma
Phase II study of lonidamine and diazepam in the treatment of recurrent glioblastoma multiforme
Current status of treatment for patients with metastatic prostate cancer
Additive antitumor activities of taxoids in combination with the bisphosphonate ibandronate against invasion and adhesion of human breast carcinoma cells to bone.
The bisphosphonate, zoledronic acid, induces apoptosis of breast cancer cells: evidence for synergy with paclitaxel
Effects of alendronate and taxol on PC-3 ML cell bone metastases in SCID mice
Efficacy of pamidronate in reducing skeletal complications in patients with breast cancer and lytic bone metastases. Protocol 19 Aredia Breast Cancer Study Group
Reduction in new metastases in breast cancer with adjuvant clodronate treatment.
Bisphosphonates and breast carcinoma: present and future
Characterization of a novel androgen-sensitive, prostate-specific antigen-producing prostatic carcinoma xenograft: LuCaP 23.
Imatinib mesylate and zoledronic acid in androgen-independent prostate cancer
Zoledronic acid significantly reduces pathologic fractures in patients with advanced-stage prostate cancer metastatic to bone
High efficacy of docetaxel with and without androgen deprivation and estramustine in preclinical models of advanced prostate cancer
Modulation of bone microenvironment with zoledronate enhances the therapeutic effects of STI571 and paclitaxel against experimental bone metastasis of human prostate cancer
Pre-publication history
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s, amid the decision Senator John McCain reminded the American individuals that he knows how to win wars. A great many people avoided these remarks, as they didn't need any more wars. By the by, here we are amidst one and we have a youthful president who is hesitant to settle on a choice to win the war, for dread that he may accomplish something disagreeable.
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Taylor Ling from androiduiux.com released yet another free tool for Android designers. This one is my favourite of them all because it is for a free tool I use all the time. Google Drive Presentations! Taylor released a Google Drive Presentations template for Android screen design / wireframe design.
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Data from: Fitness consequences of indirect plant defence in the annual weed, Sinapis arvensis
Date Published: February 11, 2015
DOI: http://dx.doi.org/10.5061/dryad.t24gg
Content in the Dryad Digital Repository is offered "as is." By downloading files, you agree to the Dryad Terms of Service. To the extent possible under law, the authors have waived all copyright and related or neighboring rights to this data.
|seed and plant characteristics in response to herbivore treatment
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|In the experiment Sinapis arvensis plants were exposed to one of four treatment: no herbivory (=ct), healthy Pieris brassicae caterpillars (=Pier), caterpillars parasitized by the gregarious Cotesia glomerata (=Cot), and caterpillars parasitized by the solitary Hyposoter eneninus (=Hyp). Plants were initially grown in the greenhouse but at the onset of flowering, they were transferred to tents placed in a garden to which pollinators were added. At this time point, the plants were exposed to the treatments. The experimental unit was a tray with 6 plants (=replicate), There were 4 replicates per treatment. When insect development was completed, we counted 1) the number of undamaged seed pods and 2) the number of damaged seed pods. Plants were then transferred to a garden in which the control plants were already present. When the seedpods had matured and dried, they were collected. Seed pods that had grown additionally were collected one month later (=new seed pods). Seeds were separated from their pods and weighed (=total seed mass in g). Per plant, cohorts of 20 seeds were weighed and their mean was calculated (=mean individual seed mass in microgram). We calculated the number of seeds per plants by dividing the weight of all seeds produced by a plant by its individual seeds mass (=number of seeds). After 2 years of storage in the dark, germination success of the seeds was determined by randomly choosing 50 seeds from each plant and allow them to germinate on wet filter paper. Germination success was calculated as the fraction of seeds that germinated out of 50. Reproductive potential was then calculated as the product of seed number and germination success. The data on the seed characteristics are in the 'seed data per tray' sheet, individual seed mass are in the sheet 'seed mass of individual seeds) and the data on the seed pods are in 'seed pods' sheet.
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