text: Preface Basic Manual About Operating Instructions Thank you for buying the "TORQUE G02" (simply called the "product" or "main unit" from here on). Before use, please read the "Setting Guide", "Notes on Usage", or "Basic Manual" (This Manual) for proper usage. ■ "Basic Manual" (This manual)/"Setting Guide" Battery pack (KYV35UAA) List of Packaged Items Battery cover (KYV35TBA) Before your start using the product, make sure that you have all the following packaged with the product. * Installed on back of main unit G02 Kyocera TV antenna cable 03 (03KYHSA) * Kyocera TV antenna cable 03 (03KYHSA) is not waterproof/dustproof. Back cover (KYV35TGA/KYV35TRA/ KYV35TKA) Main unit * Installed on back of main unit Cell Phone Etiquette • Do not listen to music or watch videos or TV while driving a car or motorbike, or riding a bicycle. Use of cell phones while driving a car or motorbike is prohibited by law. (Use of cell phones while riding a bicycle may also be punishable by law.) In addition, stay alert to the traffic around you even when walking. Surrounding sounds may not be heard clearly, and gazing at the screen might distract your attention causing a traffic accident. Be especially careful at railroad crossings, on a platform, and at pedestrian crossings. • Use of cell phones on board is restricted. Follow the instructions of each airline. microSD memory card Wireless charging pad AC adapter microUSB cable Earphones -2- ■ Note on Button Illustrations In this manual, buttons are represented by simplified illustrations as shown below. This manual gives screens and operations for the product with an au Nano IC Card 04 installed. Screen illustrations shown in this manual may look different from the actual screens. In some cases, minor details or a part of a screen may be omitted. Actual screen r (Volume UP button) l (Volume DOWN button) F C H The notations used for operation procedures in this manual are as follows. Tapping is to select a key or icon displayed on the screen by lightly tapping it with your finger. Description Explanation On the Home screen → [Phone] → [1][4][1] → [CALL] Tap " (Phone)" at the bottom of the Home ", " ", " ", then screen. And tap " tap " " (Outgoing call) at the end. In sleep mode, F In sleep mode, press F. ⑮ External connection terminal cover The opening in the cover is a necessary part of its waterproof construction. Do not poke with a pointed object or block it. Battery pack Remove the battery cover and then the battery pack to access the au Nano IC Card 04 slot and microSD memory card slot. ⑯ External connection terminal Used for connecting Common AC Adapter 05 (sold separately), microUSB Cable 01 (sold separately), etc. knob lock Built-in Bluetooth®/Wi-Fi® antenna* Photo light/Simple light Out camera (lens) f mark Hold the f mark over the reader/writer when using Osaifu-Keitai®. Send or receive data via IC transmission. Back cover Wireless charging area For wireless charging, place the center of this portion on the q mark on a separately-sold wireless charging pad. Speaker Ringtone or alarm sound can be heard from here. -4- -5- ③ Strap eyelet ⑤ ④ Earphone microphone terminal Use for connecting an earphone (commercially available), Kyocera TV antenna cable 03 (03KYHSA), etc. ⑧ ⑨ ⑤ Earphone microphone terminal cover The opening in the cover is a necessary part of its waterproof construction. Do not poke with a pointed object or block it. ⑥ In camera (lens) ① Wireless charging antenna connection ⑦ Receiver Hear the other party's voice on call, play sound of answer memo, etc. with the Smart Sonic Receiver. ⑰ ⑧ Proximity sensor/Light sensor Proximity sensor prevents from erroneous operation of touch panel during a call. Light sensor detects the ambient light level to adjust the display brightness. ⑩ ② ◎ Operations from the vertical display are mainly described. Menu items/ icons/buttons on a screen may be different from the ones in the horizontal display. ◎ Menu items/layers/icons may be different depending on functions, conditions, etc. ◎ In this manual, screenshots for body color "Green" are provided as examples. ◎ In this manual, "microSD™ memory card", "microSDHC™ memory card" and "microSDXC™ memory card" are abbreviated as "microSD memory card" or "microSD". ◎ All of the indicated amounts exclude tax unless otherwise specified. ⑨ Incoming (charging) light Lights in red while charging. Blinks in green for an arriving call or new mail. ⑱ ⑪ ⑫ ⑬ ③ ⑩ Display (touch panel) ⑲ ⑪ C Back button Return to the previous screen. ⑫ H Home button Display the Home screen or use for canceling sleep mode. Long-touch to activate "Google". ⑭ ⑮ ⑬ N Recents button Show recently-used applications. ⑭ Microphone Transmits your voice to the other party during a call. Or used for recording the voice sound. Take care not to cover the microphone with your fingers during a call or recording a video. ⑯ -8- -9- Open battery cover Attaching a Battery Pack ■ Note • Reproduction of the content of this manual in part or in whole is prohibited. • The content of this manual is subject to change without notice. • Every effort has been made in the preparation of this manual. Should you notice any unclear points, omissions, etc., feel free to contact us. ② z Direct button The function assigned to the direct button is activated. ④ ⑦ * "The Company" as appears in this manual refers to the following companies: Sold by: KDDI CORPORATION, OKINAWA CELLULAR TELEPHONE COMPANY Manufactured by: KYOCERA Corporation ① d Volume UP/DOWN button Adjusts sound volume. Press and hold l (Volume DOWN button) on left side to set "Silent mode". ⑳ Names and Functions of Parts ⑥ Lift the battery cover at the ▼ mark at its bottom right (use fingernail, etc.) Remove the back cover of the back side of the product - 10 - - 11 - Insert tabs on battery cover in slots on product and close battery cover ② Lift the back cover by the notch at its bottom (use fingernail, etc.) in the direction shown to remove. Fit back cover to product, then press firmly where shown from ① to ⑤ making sure there are no gaps all around back cover ① ③ microSD memory card slot ② ④ au Nano IC Card 04 slot * Do not cover antennas with your hand or put stickers etc. It might affect communication quality. ◎ Do not place stickers, etc. over proximity sensor/light sensor. ◎ Product is equipped with an atmospheric pressure sensor. You can display barometric pressure and elevation when using a barometric display app, however, values are not absolute due to a number of variables, and are approximate only. ◎ Do not remove film sheet from atmospheric pressure sensor inlet/ adjustment area or microphone opening. ① ③ ⑤ Wireless charging antenna*/charging connection area ① ② ⑤ Microphone opening ④ Press along cover where shown from ① to ②, making sure there are no gaps all around battery cover ⑳ Built-in GPS antenna* Built-in sub antenna* When Using the Product Before using the product, be sure to read the "Notes on Usage" for proper usage. Before you assume that the product is malfunctioning, check for possible remedies in the following au Customer Support site of au homepage: http://www.au.kddi.com/english/support/) ( * Unless specified otherwise, steps describe operations using onscreen keys. -7- ⑲ Options port You can download the English version of the Basic Manual from the au website. Download URL: http://www.au.kddi.com/english/support/manual/) ( Notations used in this manual N ■ Description of Operations for Selecting Item/Icon/ Button etc. -6- ⑱ k Camera button Press and hold to activate camera. Also use as shutter for still photos and underwater camera screen. ■ Downloading Manuals z (Direct button) ■ Consider people around you! ⑰ F Power button Power ON/OFF, activate/deactivate Sleep mode, etc. You can use the "Instruction Manual application" (Japanese) on the product to confirm detailed operational procedures. Certain functions can be directly activated from the application screens on which their operations are described. Home screen → [Apps] → [取扱説明書 (Instruction Manual)] Also, you can use the "Instruction Manual application" (English version) on the product to check operational procedures. Home screen → [Apps] → [Basic Manual] • To use the applications for the first time, you need to download and install them by following on-screen instructions. In this manual, some icons on a screen are omitted. k • To prevent ringtone from bothering other people, not only refrain from making a call but also power off or use Silent mode at a movie theater, theater, museum, library, etc. • In a city area, use in a place where you do not bother people walking. • It is extremely dangerous to walk while looking at the screen of the cell phone. Do not make calls or operate a cell phone while walking or by stopping suddenly. • Move to a place where you do not disturb others while you are in shinkansen, a hotel lobby, etc. • Be careful not to be loud while talking. • Be careful of sound leakage from earphones in trains or other places with many people around you. • Ask permission if you take photos with your cell phone camera. • There may be a person with a cardiac pacemaker nearby at a place filled with people such as in a crowded train. Set "Airplane mode" or turn off beforehand. • When a medical institution has laid down designated areas where use of the product is prohibited or is not allowed to be brought in, abide by the instructions of that medical institution. ■ "Instruction Manual Application" (Japanese/English) • It is recommended you keep a copy of important data in your PC's hard disk, etc. Whatever the cause of fault or malfunction may be, the Company assumes no responsibility for alteration or loss of saved information. • Contents saved in the product, such as contacts, mails and favorites, might be altered or lost in an accident, fault, repair or mishandling. Be sure to keep a copy of important contents. Note that Company assumes no responsibility for any damages or lost profits resulting from altered or lost contents. • Note that content data (both charged or free content) saved with the product cannot be returned to the customer when the product is replaced for repair of a fault, for example. • The product uses liquid crystal for its display. The display response speed may become slow when the ambient temperature is low, which is due to the property of liquid crystal and not a malfunction. Display response speed will return to normal at room temperature. • Although the display used on the product is made using high-precision technology, some pixels (dots) might be lit or out at all times. This is not a malfunction. • You are recommended to store copies of individual data such as photos you took, videos and music on your PC by sending each file as mail attachment, etc. Note, however, that you may not be able to make copies of any copyrighted data even by the above-mentioned means. • Do not discard the product together with regular trash. Please cooperate in the collection of the product when it is no longer needed to protect the environment and effectively use resources. Old product is collected at au shops and other places. -3- ■ Notes on Illustrations/Screenshots Notations Used in This Document ■ Use of the product is not allowed in the following places! • • • • • ◎ Purchase a specified charger (sold separately). ◎ The illustrations of cell phone in the manual are used only for explaining. They may differ from the actual product. -1- May 2015, 1st Edition • 取扱説明書 (Basic Manual) (Japanese) • ご利用にあたっての注意事項 (Notes on Usage) (Includes warranty) (Japanese) • 設定ガイド (Setting Guide) (Japanese) The following items are not included in the package. Handles only basic operations for main features. For detailed descriptions on various functions, refer to the "Instruction Manual application" (Japanese) installed on the product or "取扱説明書 詳細版 (Full Instruction Manual)" (Japanese) available on the au homepage. http://www.au.kddi.com/support/mobile/guide/manual/) ( • Company names and product names referred to in this manual are trademarks or registered trademarks of respective companies. • Communication is not possible even inside the service area in places where the signal does not reach (e.g. tunnels and basements). Also, communication is sometimes not possible in poor reception areas. Communication is sometimes interrupted if you move into a poor reception areas during communications. • Since this product uses radio waves, the possibility of communication intercepts by third parties cannot be eliminated. (Though LTE/WiMAX 2+/ GSM/UMTS system has highly secure confidential communication features.) • When connecting to emergency services in Japan, use au VoLTE (LTE network). You cannot connect through 3G (circuit switching network). • This product is compatible with the international roaming service. Each network service described in this manual varies depending on the area and service content. • Since this product is a radio station under the Radio Law, you may be asked to temporarily submit the product for inspection in accordance with the Radio Law. • IMEI information of your cell phone is automatically sent to KDDI CORPORATION for maintenance and monitoring operational status of your cell phone. • Before you start using the product overseas, check the relevant laws and regulations of the country/region you visit. • The Company is not liable for any damages arising from earthquakes, lightning, storms, floods or other natural disasters, as well as fires, actions by third parties, other accidents, intentional or mistaken misoperation by the customer, or use under other unusual conditions outside the responsibility of the Company. • The Company is not liable for any incidental damages (change/ disappearance of described content, loss of business income, disruption of business, etc.) arising from use or inability to use the product. • The Company is not liable for any damages arising from failure to observe the described content of this manual. • The Company is not liable for any damages arising, for example, from malfunction caused by combination with connected devices or software not related to the Company. • Captured image data or downloaded data may sometimes be altered or lost due to faults, repair or other handling of the product. The Company is not liable for any damage or lost income resulting from recovery of these data. Notch Confirm location of connection, and then slide battery pack in and press firmly into place Battery cover ② Make sure tab is visible on top. Battery pack Slide knob lock in direction of "UNLOCK" ① Connection Slide knob lock in direction of "Lock" to lock firmly If knob lock is not locked, the back cover cannot be closed. Attaching/Removing a Battery Pack ◎ Be sure to check the au Nano IC Card 04 is certainly attached and then attach the battery pack. ◎ Improperly attaching parts may damage the battery pack or attaching the battery cover. ◎ When attaching the battery cover, be careful that the battery pack tab is not sticking out. May allow water seepage. ◎ To ensure back cover will close, always slide the knob lock to "LOCK" to firmly lock after closing the battery cover. Use the battery pack for this product and attach it properly. Built-in WiMAX 2+ antenna* Built-in main antenna* Atmospheric pressure sensor inlet/adjustment area NFC (FeliCa compatible) antenna* ◎ Before attaching/removing the battery pack and battery cover, turn the power off. Battery cover - 12 - - 13 - Removing a Battery Pack Removing the au Nano IC Card 04 Remove back cover, battery cover (▶P.14) Pull battery pack up by tab and remove Battery pack - 14 - Tab ◎ Before attaching/removing au Nano IC Card 04, be sure to remove a power plug of specified AC adapter etc. from the product. Turn the power off and remove the battery pack (▶P.18 "Removing a Battery Pack") Pull tray straight out by groove Attaching the au Nano IC Card 04 (▶P.18 "Removing a Battery Pack") ◎ When removing the battery pack, be sure to pull up by the tab. Trying to pull up from any direction other than at the tab may damage the product or the battery connection. Groove Remove au Nano IC Card 04, and reinsert tray straight in Attach back cover, battery cover (▶P.14) Groove Attaching a microSD Memory Card Confirm the direction of the microSD memory card and slowly insert it into the slot until it clicks - 16 - Removing a microSD Memory Card Turn the power off and remove the back cover and battery pack Slowly push the microSD memory card toward the slot until it clicks When a click sound is heard, pull your finger with the microSD memory card touched. Keep putting your finger on the microSD memory card until it comes out a little. Releasing the microSD memory card when pushed hard may cause it to pop out. Insert a microSD memory card until you hear a click and confirm it is locked. Releasing the microSD memory card before it is locked may cause it to pop out. microSD logo facing up Slowly remove the microSD memory card Place au Nano IC Card 04 on tray (IC (metal) part up) and push tray with au Nano IC Card 04 all the way in Attach battery pack, battery cover, and back cover (▶P.14) Note direction of notch. au Nano IC Card 04 Attaching/Removing a microSD Memory Card Turn the power off and remove the back cover and battery pack (▶P.14) Turn the power off and remove the battery pack Pull tray straight out by groove - 15 - Attach battery pack, battery cover, and back cover (▶P.14) Attach battery pack, battery cover, and back cover (▶P.14) Notch The au Nano IC Card 04 contains customer phone number and other information. The product is compatible with au Nano IC Card 04 only. You cannot use the product with an IC card other than au Nano IC Card 04. ◎ Insert a microSD memory card with the right side up in the appropriate direction. Inserting a microSD memory card forcefully into the slot could result in failure to remove the microSD memory card or damage to the microSD memory card. au Nano IC Card 04 Slowly pull the microSD memory card straight out. Some microSD memory cards cannot be unlocked and do not come out smoothly. In such case, pull it out with your finger. Attach battery pack, battery cover, and back cover (▶P.14) ◎ Do not touch the terminal part of microSD memory card. ◎ Do not remove the microSD memory card forcefully. It may result in damage to the microSD memory card or the data loss. ◎ The microSD memory card may be warm after a long time use. It is normal. - 17 - Charging When you purchase your product, the battery pack is not fully charged. Make sure to charge the battery pack before use. When the charging light in red turns off, charging is complete. ◎ The product may become warm while charging, depending on the situation, but this is not abnormal. ◎ A few seconds after charging starts, the time remaining until fully charged is displayed in the Start screen. This time is intended as a guide, and should not be taken as an accurate indication. ◎ Charging while using camera etc. may take longer. ◎ When you operate the product with the specified charger (sold separately) connected, the product may repeat short-time charging/ discharging resulting in short battery life. ◎ When temperature of environment or the product becomes extremely high or low, charging may be stopped. Try to charge the battery as far as possible at room temperature. ◎ If the charging light blinks in red, check if the battery pack is correctly attached or connected. Even if the light keeps blinking, stop charging and then contact an au shop or Keitai Guarantee Service Center. ◎ Firmly close the external connection terminal cover after charging to prevent water or dust from getting in. And do not pull strongly or twist the cover. ◎ If charging is stopped while the charging light is still turned on, the battery may not be fully charged even with " " (Full) displayed. In that case, available time will be short. ◎ Do not wirelessly charge when a specified AC adapter (sold separately) or microUSB Cable 01 (sold separately) are connected. In addition to not charging properly, malfunction may also result. ◎ Do not allow conductive foreign objects (metal fragments, pencil leads, etc.) to come into contact with or get inside the connection terminals. IC (metal) part - 18 - - 19 - - 20 - - 21 - - 22 - - 23 - ◎ The magnetic field produced during charging may prevent the magnetic sensor from working properly. Charging with a Wireless Charging Pad (Sold Separately) Connect the DC connector of the special AC adapter into the DC jack on the Wireless Charging Pad 01 (sold separately) and plug the special AC adapter into an outlet (AC 100 V - 240 V) * With this product, the charging indicator on the Wireless Charging Pad 01 (sold separately) continues to be blue even after charging completes. For further details on charging indicator display patterns or charging conditions, see the instructions included with the Wireless Charging Pad 01 (sold separately). DC connector Check the orientation of the microUSB plug of Common AC Adapter 05 (sold separately) and insert it straight into the external connection terminal ◎ If you move the product from where the charging indicator first lights blue, it may not charge or charging may take a long time. Remove the product and place it again after about 15 seconds where the charging indicator is blue. ◎ If charging does not start, check that the battery cover is properly attached. Also check that the charging connection under the battery cover is not soiled. Charging with a Specified AC Adapter (Sold Separately) Charging light Simply placing the product on top of an au-specified wireless charger product (sold separately) displaying the mark on the left allows charging without the need to connect a cable. Be sure to also read the instructions for any supported product. Products with the mark are compliant with the wireless charging specifications of the Wireless Power Consortium (WPC). This product supports "おくだけ充電 ® (okudake juden)" place-and-charge functionality. "おくだけ充電" and the "おくだけ充電" logo are registered trademarks of NTT DOCOMO, INC. Check that the charging indicator is blue, and that the product's charging light is red. If the charging indicator is red, the product is not placed where it can charge; adjust the product's position. Once charging completes, the charging light goes out. Wireless Charging Pad 01 (sold separately) How to use the Wireless Charging Pad 01 (sold separately) for charging is explained here. For usage precautions and details, also see the instructions included with the Wireless Charging Pad 01 (sold separately). q Place the product, with its wireless charging area downward and centered on the q mark on the Wireless Charging Pad 01 (sold separately) Close the external connection terminal cover Pull out the power plug of Common AC Adapter 05 (sold separately) from the outlet ◎ Note that applying unnecessary force with the external connection terminal connected to the external device might cause damage. ◎ When charging starts with the battery empty, the charging light may not light immediately. But charging has started. With the projection facing down Charging with Common AC Adapter 05 (sold separately) is explained. For information on specified AC adapters (sold separately), see "Related Accessories" (▶P.42). Special AC adapter included with Wireless Charging Pad 01 When charging ends, pull out the microUSB plug of Common AC Adapter 05 (sold separately) straight from the external connection terminal Open the external connection terminal cover of the product Common AC Adapter 05 (sold separately) DC jack Insert the power plug of Common AC Adapter 05 (sold separately) into an outlet (100 VAC to 240 VAC) Check that the charging light on the product lights in red. When the battery power turns on, " " appears on the status bar. When charging ends, the charging light turns off. Wireless charging area Charging indicator Once charging completes, remove the product, and unplug the special AC adapter Common AC Adapter 05 (sold separately) - 24 - - 25 - Turning the Power On/Off - 26 - • If Smart Lock is set, tapping " " at screen top temporarily cancels Smart Lock, and the screen for the security feature you have set is displayed. • If a description for the Home screen appears, read the information and tap "OK". Force Shutdown and Restarting Force shutdown and restart the product when the screen freezes or the power cannot be turned off. Turning the Power On F (press and hold for at least 2 seconds) The Start screen is displayed (▶P.31 "The Start Screen"). • For the first time the product turns ON, the initial settings such as "au Easy Setting" activate. Make the settings as required. ◎ While logos are displayed after the power is on, initial settings for touch panel are in process. Do not touch the screen. The touch panel may not work properly. ◎ "au Easy Setting" can be set up later even though it is skipped. ◎ If the charging light blinks in yellow when you turn the power on, the remaining battery is not sufficient for activating the product. Charge the battery before use. Turning the Power Off F (press and hold for at least 11 seconds) ① Widget When you purchase the product, the Dura Clock & Weather widget is displayed. • Swipe (flick) to the left or press z (Direct button) to switch to the Compass/ Barometer/Tide widget. • To delete a widget, long-touch the widget → Drag to "Remove" at screen top. ① ◎ If the product is forced shutdown and restarted, unsaved data will be erased. Do not force shutdown except when the product becomes inoperative. ② Switching to English Display ③ You can switch the display from Japanese to English. Home screen → [アプリ一覧 (Apps)] → [設定 (Settings)] → [言語と入力 (Language & input)] → [言語 (Language)] → "English" ④ 《Start screen》 "Power off" → "OK" " to ④ Start icon The Start screen is displayed when you turn the power on or cancel sleep mode. Sleep Mode The Start screen is displayed (▶P.31 "The Start Screen"). • The first time activating, a description of the Start screen is displayed. Read the information and tap "OK". Description Alarm set ⑥ Notification area You can check the status of the product or details of notification. For some information, tap to activate the corresponding application. Silent mode (Vibrate) set Silent mode (Mute) set Bluetooth® in use standby/ connected Auto Answering set set/ full * In Japan, you can use "LTE" and "WiMAX 2+" networks. "4G" is displayed for both networks. According to the signal congestion etc., the product is connected to the less congested network. Notification Panel Slide the status bar down to display the notification panel and on/off icons, where you can check notifications and activate corresponding applications as well as quickly set frequently used functions on/off. In the Address Book Plus display, display contacts in "Favorites" and "Recent Calls". Use with your preferred setting. ① ① Setting menu icon Tap " ② On/off icons Enable/Disable frequently-used functions. ② ③ ③ ⑤ ⑥ " to display the settings menu. ④ / icon Tap " / " to enlarge/shrink the on/ off icons area. ④ Edit icon Rearrange on/off icons. ◎ You can slide the notification panel up to hide it. ◎ When a new notification arrives, a notification is displayed at screen top. ◎ If there are notifications that can be erased, tap [CLEAR ALL] at bottom right of screen. Displaying a Menu There are two types of methods to display a menu screen; by tapping " and by long-touching entry field or item. Using the au Disaster Countermeasure Application au災害対策 (au Disaster Countermeasure) menu screen → [災害関連情報 (Disaster Information)] Follow the onscreen instructions ■ Battery Pack (KYV35UAA) ■ Back cover (KYV35TGA/KYV35TRA/KYV35TKA) ■ Battery cover (KYV35TBA) ■ Kyocera TV antenna cable 03(03KYHSA) ■ Common AC Adapter 05 (0501PWA) (sold separately) ■ Common AC Adapter 03 (0301PQA) (sold separately) ■ Common AC Adapter 03 Navy (0301PBA) (sold separately) ■ Common AC Adapter 03 Green (0301PGA) (sold separately) ■ Common AC Adapter 03 Pink (0301PPA) (sold separately) ■ Common AC Adapter 03 Blue (0301PLA) (sold separately) ■ AC Adapter JUPITRIS (White) (L02P001W) (sold separately) ■ AC Adapter JUPITRIS (Red) (L02P001R) (sold separately) ■ AC Adapter JUPITRIS (Blue) (L02P001L) (sold separately) ■ AC Adapter JUPITRIS (Pink) (L02P001P) (sold separately) ■ AC Adapter JUPITRIS (Champagne) (L02P001N) (sold separately) ■ au Carrying Case G Black (0106FCA) (sold separately) ■ Wireless Charging Pad 01 (0101PUA) (sold separately) ■ Portable Charger 02 (0301PFA) (sold separately) ■ microUSB Cable 01 (0301HVA) (sold separately) ■ microUSB Cable 01 Navy (0301HBA) (sold separately) - 42 - Before you assume that the product is malfunctioning, check the following: Symptom Cannot turn on power. Cannot charge the battery pack. What you should check Page Is the battery pack charged? P.23 Is the battery pack attached properly? P.14 Are the terminals of the battery pack dirty? P.18 Is F pressed and held? P.30 Is the specified charger (sold separately) properly connected? P.23 Is the battery pack attached properly? P.14 Is the temperature of the product or battery pack high or low? Charging may stop due to the temperature of the product or battery pack. P.23 Are the specified accessories (adapter, etc.) used to charge? P.27 - 43 - ③ Indicator Check current position in the Apps list. Displayed when high quality sound call with au VoLTE compatible phone au災害対策 (au Disaster Countermeasure) menu → [緊急速 報メール (Emergency Rapid Mail)] Inbox appears. Select a mail you want to view to check the detail. 削除 (Delete) Delete received mail. 設定 (Set) Make settings for Earthquake Early Warning and Disaster and Evacuation Information. 受信設定 (Receive settings): Set whether to receive Earthquake Early Warning / Disaster and Evacuation Information. 音量 (Volume): Set the volume of the alert tone. マナー時の鳴動 (Alarm in Silent mode): Set whether alarm sounds in Silent mode. バイブ (Vibration): Set whether the phone vibrates when a warning/information is received. 受信音/バイブ確認 (Alert tone/vibration check): Check operation of the alert tone and vibration. 緊急地震速報 (Earthquake Early Warning) Symptom What you should check Page Symptom Is the product placed in the correct orientation and within a chargeable area on the Wireless Charging Pad (sold separately)? P.26 Cannot make calls. Is the power turned on? P.30 Is your au Nano IC Card 04 inserted? P.19 Is another object placed between the product and the Wireless Charging Pad (sold separately)? P.26 Cannot receive calls. Is signal strong enough? P.35 Is the product out of the service area? P.35 Is the power turned on? P.30 Are the Wireless Charging Pad (sold separately) and special AC Adapter properly connected? P.25 Is your au Nano IC Card 04 inserted? P.19 Is the product out of the service area or in an area where the signal is weak? P.35 Is the product or battery at a high/low temperature? Charging may stop depending on the temperature. P.23 Is the built-in antenna covered with finger etc.? P.12 P.14 Is a card other than au Nano IC Card 04 inserted? P.18 Is the battery cover properly attached? The charging indicator is still lit after completing charging, but this is not abnormal. Check the display on the phone. P.26 Cannot operate button/touch panel. Is the power turned on? P.30 Turn off the power and then turn it on again. P.30 Is the phone or battery at a high/low temperature? Charging sometimes takes a long time depending on the temperature. ― Cannot operate the touch panel as intended. Check the correct way to operate the touch panel. ― Charging while using the product can also cause charging to take a long time. ― Press and hold F for 11 seconds or longer to force shutdown and restart. P.31 The power goes off. Is the battery pack fully charged? P.23 The power is going off while the activation logo is displaying. Is the battery pack fully charged? P.23 Update available 《Apps list》 New OS update or software update " " (out of service area) appears. " ■ Examples of main status icon Icon Description Time ◎ The service is available only in Japan (it cannot be used overseas). ◎ No information fee or communication charge is required for receiving Emergency Rapid Mail. ◎ You cannot receive Emergency Rapid Mail when your cell phone is turned off. ◎ Emergency Rapid Mail may not be received if you are in a place where signal does not reach even in the service area (e.g. in a tunnel, basement) or in a place with a poor reception. ◎ You cannot receive Emergency Rapid Mail that the reception is failed. ◎ Reception of Emergency Rapid Mail is notified by a special warning tone and vibration. It is not possible to change the warning tone. Battery level 100%/ empty/ charging Signal strength/Signal condition (LTE/WiMAX 2+) level 4/ out of range/ in communication LTE/WiMAX 2+ available*/ Roaming (Communication mode according to the network is also shown) * Reception of Earthquake Early Warning is notified by a special warning tone, voice ("地震です (Jishin-desu)" (An earthquake)) and vibration. " appears. What you should check Page Turn the power off and then back on. P.30 Place the product in sleep mode and then cancel sleep mode. P.33 Is your au Nano IC Card 04 inserted? P.19 A message such as charge the battery appears. The battery is almost dead. P.23 Cannot connect to the party and the phone beeps even though a call is made. Is the product out of the service area or in an area where the signal is weak? P.35 The wireless line is extremely busy or the party is calling. Retry later. - 45 - - 35 - ◎ Earthquake Early Warning may not arrive before strong tremors in arrears near the epicenter. ◎ This delivery system is different from Earthquake Early Warning provided through TV, radio, or other communication procedures, which means that the time the Earthquake Early Warning arrives may vary. Tsunami Warning ◎ Tsunami Warning is a notification delivered from the meteorological bureau (major tidal wave, seismic sea wave) to the area including target coast. Disaster and Evacuation Information ◎ Disaster and Evacuation Information is a service that distributes bulletins concerning residents' safety including evacuation advisories, evacuation orders and other warnings issued by the national and local governments. Using the Disaster Voice Messaging Service ◎ When you receive Emergency Rapid Mail during a call, the warning tone does not sound. ◎ Information from someplace other than your current location may be received. ◎ KDDI is not liable for damages suffered by customers resulting from the service's information, lack or delay in the information caused by transmission or system breakdowns, or other events that are outside the responsibility of KDDI. ◎ Refer to the Japan Meteorological Agency web page for details about distribution of Earthquake Early Warning. http://www.jma.go.jp/) ( Earthquake Early Warning ◎ Earthquake Early Warning is sent to areas where strong quakes (over 4 degrees) are expected when the earthquake whose the maximum seismic intensity 5 lower is anticipated occurs. ◎ Immediately after an earthquake occurs, quakes (P waves and initial tremors) near the epicenter are detected and position, scale, and expected strength are automatically calculated and notification is sent as soon as possible within a few seconds to tens of seconds before the strong quakes (S waves and major tremors) caused by the earthquake start. Disaster Voice Messaging Service is a service which allows you to record your voice and send someone you want to inform your well-being in case of a large-scale disaster. - 40 - - 41 - Updating Software or the OS You can update the product to the most recent software for optimal performance and to get the latest enhancements. There are several methods to update software. • Download software to the product to update • Use Wi-Fi® to download software to the product and update ■ Notes au災害対策 (au Disaster Countermeasure) menu screen → [災害用音声お届けサービス (Disaster Voice Messaging Service)] Follow the onscreen instructions to register. ◎ For use over Wi-Fi®, it is necessary to carry out initial setting over 4G (LTE/WiMAX 2+) network. ◎ Voice message can be recorded for up to 30 seconds. ◎ Messages can be sent and received to or from au cell phones, other network operators' cell phones and PHS. ◎ Voice message may be difficult to hear if the media volume is low or Silent mode is set. ◎ Saving or playing voice messages may fail if a phone does not have available memory. Downloading and Updating Software or the OS Update files can be downloaded from the Internet web site into the product directly. Apps list → [Settings] → [About phone] → [Software update] [CHECK FOR UPDATE] From here on, follow the onscreen instructions. • You are charged for data communication when connecting to the Internet from the product using packet communication. • Information is provided such as through the au homepage when a software update is required. For details, inquire at an au shop or Customer Service Center (157/no charges). au may also inform customers using a product that a software update is required in order to enjoy better usage of the product. • You are recommended to back up your data before updating software. • Fully charge before update. If the update is started with the battery power low or battery power becomes low during update, software update cannot be done. • Check the radio wave condition. Software update may fail in poor reception area. • Any operations are not available during software update. Calling 110 (Police), 119 (Fire/Ambulance), 118 (Maritime rescue) is not available. Alarm does not work, either. • If software update has failed or stopped, perform the same procedure again. • Update is unavailable during international roaming. • If you fail to update software, it may become impossible to operate the product. If this happens, bring it to an au shop or PiPit (not accepted by some shops). ◎ Note that depending on your subscription contract, communication fees may be incurred when your phone automatically searches for an available network. ◎ After a software or OS update, the product cannot be returned to the original version. After-Sales Service ■ When asking for repair For repair, contact Keitai Guarantee Service Center. During the warranty period Repairs will be done based on the terms of services of the free-of-charge repair warranty described on the warranty card. Outside the warranty period We shall repair the product for a charge as requested by the customer if repair renders it usable. ― ◎ Before handing in the product for repair, make a backup of the contents of memory since they may disappear during repair. Note that the Company shall not be liable for any damages and loss of income should the contents of memory be altered or lost. If you cannot find the solution to your problem in the above items, refer to the au homepage or au Customer Support on the website shown below. http://www.au.kddi.com/english/support/) ( - 44 - New message Installation completed - 39 - Cannot operate/ The screen freezes/Cannot turn off power. Making a call, calling, receiving a call - 34 - Cannot charge with the Wireless Charging Pad (sold separately). Charging does not complete with the Wireless Charging Pad (sold separately). Music playing Using Emergency Rapid Mail - 38 - Troubleshooting TV activated au Nano IC Card 04 uninserted 災害・避難情報 (Disaster and Evacuation Information) Related Accessories New calendar event notification ② Menu icon Displays a menu for the Apps list. Notification icons appear on the left of the status bar, showing missed calls, new mail, operations in progress, etc., and status icons appear on the right, showing the status of the product. Emergency Rapid Mail is a service that distributes Earthquake Early Warning or Tsunami Warning delivered from the meteorological bureau or Disaster and Evacuation Information delivered from the government or local public organization to all au cell phones in specified areas simultaneously. When you purchase the product, "受信設定 (Receive options)" of the Emergency Rapid Mail is set to "受信する (Receive)". Reception setting of Tsunami Warning is available in the settings of Disaster and Evacuation Information. When you receive Earthquake Early Warning, ensure your safety and take proper action according to the situation around you. When you receive a Tsunami Warning, draw away from sea coast immediately and evacuate to safe place such as upland or well-built high building. ◎ To register information of well-being, E-mail address (∼ezweb.ne.jp) is required. Set up E-mail address beforehand. ◎ Deleting or changing the setting for information of well-being is unavailable during Wireless LAN (Wi-Fi®) connection. ◎ The Company makes no guarantees about the quality of this service. The Company is not liable in the event of any nonconformities about registration of well-being information or damages by loss of well-being information arising from intense access to this service or equipment failure or damages caused by registered well-being information. ◎ With Portable Charger 02 (sold separately), it may not be possible to adequately charge the product. ◎ For the latest information on accessories, visit the au homepage (http:// www.au.kddi.com/english) or contact the Customer Service Center. ◎ Accessories on this page can be purchased from au online shop (http:// auonlineshop.kddi.com/). Some accessories may not be purchased due to the availability. Snoozed alarm/stopped alarm (still set) 《Home screen》 au災害対策 (au Disaster Countermeasure) menu appears. When activating the application for the first time, the agreement for use and initial settings appear. Follow the onscreen instructions. ■ microUSB Cable 01 Green (0301HGA) (sold separately) ■ microUSB Cable 01 Pink (0301HPA) (sold separately) ■ microUSB Cable 01 Blue (0301HLA) (sold separately) New Emergency Rapid Mail Airplane mode is set Apps list → [au災害対策 (au Disaster Countermeasure)] Using Disaster Information You can check history of Disaster and Evacuation Information delivered by local government, disaster information portal, etc. Using the Disaster Message Board Follow the onscreen instructions to register/confirm. New mail message (Gmail) ③ - 33 - au災害対策 (au Disaster Countermeasure) menu screen → [災害用伝言板 (Disaster Message Board)] New mail message (E-Mail) ① Category name Tap to display navigation. • You can also display navigation by sliding or flicking the left edge of the screen to the right. Icons ⑤ Apps list ② ③ ④ ⑤ - 37 - ② Monitoring the Product's Status ④ Quick launch area The au Disaster Countermeasure application allows you to use the Disaster Message Board, Emergency Rapid Mail (Earthquake Early Warning, Disaster and Evacuation Information, Tsunami Warning), Disaster Voice Messaging Service, and Disaster Information. - 36 - ◎ Some cell phones do not support receiving voice messages. For details, refer to au homepage. " New mail message (SMS) The Apps list appears. The first time opening the Apps list, instructions for selecting apps appears. Read the instructions and tap "OK". ① Description Missed call ① Status bar ① Disaster Message Board service enables you to register information of well-being from an area of distress via LTE NET in case of large-scale disaster such as earthquake with a seismic intensity of over 6 lower. Registered information can be viewed on any cell phones and PCs besides by au cell phone users. For details, refer to "Disaster Message Board" of au homepage. Icon Available phone memory low The Home screen consists of multiple screens. Slide/flick right or left to switch them. Also, press H to go to the Home screen any time. - 32 - ⑤ Address Book Plus display Display different information registered to the address book. You can also display favorites and other contacts you call frequently. • Tap " " to change settings for the Address Book Plus display. ■ Examples of main notification icon Using the Home Screen ◎ If "Security type" is "None", the Start screen is not displayed. - 31 - - 29 - Home screen → [Apps] ◎ Do not touch the screen when pressing F and displaying the screen. The touch panel may not work properly. " and swipe (flick) toward "START" - 30 - A list of installed apps is displayed. While in sleep mode, F or H The Home screen is displayed (▶P.33). Or, the screen just before entering sleep mode is displayed. • Swiping (flicking) toward "CAMERA"/ "PHONE" activates camera/phone. • If " " is displayed at screen top, the Start screen "Security type" is set to "Pattern", "PIN", or "Password". Unlock the security feature to display the Home screen. Wi-Fi® signal strength level 4/ level 0 Using the Apps List While screen backlight is turned on, press F or leave the product for a certain period of time without any operations to turn off the screen temporarily and the product goes into sleep mode. To cancel sleep mode, operate the following steps. ③ Indicator After the Start screen is displayed, you can display the Home screen as follows. Icon - 28 - ② Shortcuts/Widgets/Folders ■ Displaying the Home screen from the Start screen Touch " ② Notification display Contacts set to Address Book Plus (▶P.36) and notifications are displayed. • Double-tap a notification to activate the corresponding application. • To not display notifications, tap "HIDE". ③ Indicator Tap " " to switch widgets, and tap " add a widget. The Start Screen F (press and hold for at least 1 second) - 27 - - 46 - - 47 - ◎ Recycled parts that meet the Company's quality standards are sometimes used for repair. ◎ Collected au cell phones by Replacement cell phone delivery service which you used before are recycled to cell phones for replacement after repairs. Also replaced parts by au after-sales service are collected and recycled by KDDI. They are not returned to customers. ◎ Instances where the product has been changed, modified, or analyzed (including software modification or analysis (including rooting, etc.) reverse-engineered, reverse-compiled, or reverse-assembled) or has been repaired at a location other than an authorized repair location designated by the company may not be covered by warranty or may prevent the product from being accepted for repairs. ■ Performance parts for repair The Company retains performance parts for repair of the product main unit and its peripherals for 4 years after discontinuation of production. "Performance parts for repair" refers to parts required for maintaining the functions of the product. ■ Warranty card At the store of purchase, thoroughly check and read the name of the retailer, date of purchase and other necessary details filled in on the warranty card, and be sure to keep it in a safe place. ■ Keitai Guarantee Service Plus LTE An after-sales service membership program on a monthly basis called "Keitai Guarantee Service Plus LTE" (monthly fee: 380 yen, tax excluded) is available for using your au cell phone for a long time without worries. This service expands coverage for many troubles including malfunction, theft and loss. For details of this service, refer to au homepage or contact Keitai Guarantee Service Center. Online Repair Desk (24 hours a day over the Internet) ◎ You can apply for membership only at the time of purchasing your au cell phone. ◎ Once you cancel the membership, you cannot reapply for it until you purchase an au cell phone next time. ◎ Note that when changing the model or purchasing an extra cell phone, this service only covers the most recently purchased au cell phone. ◎ When an au cell phone is handed over to you or someone else, the "Keitai Guarantee Service Plus LTE" membership is also handed over to the successor of the cell phone. ◎ When you get a new au cell phone by changing the model or purchasing an extra cell phone, the "Keitai Guarantee Service Plus"/"Keitai Guarantee Service Plus LTE" membership for the old au cell phone is automatically canceled. ◎ Service contents are subject to change without notice. ■ au Nano IC Card 04 Members Replacement cell phone delivery service Spontaneous failure Spontaneous failure From a land-line phone/an au cell phone, 0120-925-919 (toll free) Business hours 9:00 - 21:00 (7 days a week) Holding over and repair 1st year 2nd year or later Partially damage, water soak, irreparable damage, theft or loss If you are unsure about anything regarding after-sales service, contact the following service contact. Keitai Guarantee Service Plus (for loss, theft, damage) Keitai Guarantee Service Plus LTE Service ■ After-sales service From a land-line phone, 0077-7-113 (toll free) From an au mobile phone, 113 without area code (toll free) Business hours 24-hour (7 days a week) Replacement cell phone delivery service ◎ When you have trouble with your au cell phone, replacement cell phone (same model, same color, including new battery) is delivered by calling to. Return your damaged cell phone within 14 days after replacement cell phone is delivered. ◎ Available up to twice in a year from the day you use this service as a start day. If you do not use this service in the past year for the subscription to this service, it will be 1st and if you use, it will be the 2nd. ■ au after-sales service information The au Nano IC Card 04 is lent to you by au. In case of loss or damage, the card will be replaced at your expense. When a malfunction is suspected, or in case of theft or loss, contact an au shop or PiPit. Customer Service Center (for service canceling procedure in case of loss or theft) Main Specifications (https://cs.kddi.com/support/n_login.html) • The Application for the Internet acceptance, if "damage", "wet", "theft" and "loss" are eligible. In the case of spontaneous failure (not the cause damage, such as water wet, but does not power on, the screen does not function or other), it will be accepted by phone for interview is required. • To apply for the Internet, you need the e-mail address. Others Free of charge Customer charge 1st: 5,000 yen 2nd: 8,000 yen 1st year Free of charge 2nd year or later Free of charge (three-year warranty) Partially damage Customer charge Upper limit: 5,000 yen Water soak, irreparable damage Customer charge 10,000 yen Theft, loss No recompense No recompense Free of charge Actual cost SIM-Unlocking Your au Phone This product can be SIM-unlocked. SIM-unlocking the product allows other-carrier SIM cards to be used with it. • Requests can be made for SIM-unlocking on the au homepage or at an au shop. • Some services, functions, etc. may have restrictions when an other-carrier SIM card is used. The Company does not guarantee operation whatsoever. • To SIM-unlock the product, display the Apps list → [Settings] → [About phone] → [SIM card status]. From here on, follow the onscreen instructions. • For details, refer to the au homepage. No recompense (model change) For inquiries, call: Customer Service Center For general information, charges, and operation assistance (toll free) Business hours: 9:00 to 20:00 (7 days a week) From fixed-line phones: 0077-7-111 From au cell phones: 157 area code not required Pressing "zero" will connect you to an operator, after calling "157" on your au cellphone. For service cancelation procedure in case of loss or theft (toll free) Business hours: 24 hours (7 days a week) From fixed-line phones: 0077-7-113 From au cell phones: 113 area code not required In case above numbers are not available, call toll-free: 0120-977-033 (except Okinawa) 0120-977-699 (Okinawa) Keitai Guarantee Service Center For loss, theft or damage (toll free) Business hours: 9:00 to 21:00 (7 days a week) From fixed-line phones/au cell phones: 0120-925-919 Cell phone and PHS operators collect and recycle unused telephones, batteries and battery chargers at stores bearing the logo regardless of brand and manufacturer to protect the environment and reuse valuable resources. Sold by: KDDI CORPORATION, OKINAWA CELLULAR TELEPHONE COMPANY Manufactured by: KYOCERA Corporation - 49 - - 50 - - 51 - Approx. 4.7 inches, Approx. 16,770,000 colors, Transparent TFT (IGZO) 1,280 x 720 dots (HD) Weight Approx. 203 g (with battery pack) Charging times (estimate) Wireless Charging Pad 01 (sold separately) Approx. 280 minutes Common AC Adapter 05 (sold separately) Approx. 140 minutes In Japan Approx. 1,320 minutes Overseas (GSM/ UMTS/LTE) Approx. 760 minutes In Japan Approx. 690 hours Overseas (GSM/ UMTS/LTE) Approx. 750 hours * For details, refer to au homepage. Holding over and repair ◎ Damages and malfunctions intentionally caused by the customer as well as those due to modification (e.g. disassembly, change of parts, painting, etc.) by the customer are not covered by this service. ◎ You cannot receive a refund for replacement of the outer casing due to stains, scratches, paint removal, etc. on the outer casing. * Charge amounts are all tax excluded. - 48 - Display Continuous call time Continuous stand-by time Continuous tethering time Approx. 790 minutes Maximum number of Wi-Fi tethering connection devices 10 Dimensions (W x H x D) Approx. 72 mm x 147 mm x 14.2 mm (thickest part approx. 17 mm) Internal memory*1 ROM: Approx. 16 GB RAM: Approx. 2 GB Number of effective pixels: Out-camera Approx. 13,000,000 pixels Number of effective pixels: In-camera Approx. 5,000,000 pixels - 52 - Wireless LAN (Wi-Fi®) function IEEE802.11a/b/g/n/ac compatible Bluetooth® function Bluetooth® standard Ver.4.1 compatible*2 Compatible version Output Class1 Communication range*3 10 m Supported Bluetooth profile*4 Bluetooth LE GATT/SPP/A2DP/ AVRCP/HSP/HFP/OPP/PBAP/HID/ PAN/PAN-NAP/PAN USER/HOGP/ MAP/SCMS-T/DUN*5 Frequency bands Continuous 1Seg watching time 2,402 - 2,480 MHz Approx. 11 hours 40 minutes *1 Since the storage is shared by data and applications, storage space may be reduced depending on the usage of applications. *2 It is confirmed that the product and all Bluetooth® devices are compliant with Bluetooth® standards designated by Bluetooth SIG, and they are authenticated. However, procedures may differ or data transfer may not be possible depending on the device's characteristics or specifications. *3 Changes according to objects obstructing devices and signal reception. *4 Specifications provided in Bluetooth® standards for making communication between Bluetooth®-compatible devices in accordance with their intended use. *5 The profile supports part of car navigation systems. Refer to the au homepage for use. ◎ The continuous talk time and continuous standby time may drop to less than half depending on the battery charging status, usage environment such as temperature, reception condition at the location where the product is used, and the function settings. - 53 -


text:
Better late than never. Some things that I am thankful for this year and always.
1. The opportunities that I have been given in this life.
2. People who believe in me.
3. People to believe in.
4. My husband for loving me unconditionally.
5. My beautiful kitties.
6. My family near and far, old and young.
7. My friends near and far, old and new.
8. Christmas fast approaching.
Happy Thanksgiving to all and to all a Good Night!

subset: commoncrawl


text:
Kings General Manager Dean Lombardi resolved to be patient during the 1-4-2 slide that followed his team's 5-1-1 start, cutting players slack while they got accustomed to new teammates and overcame jet lag after their European opener.
"I didn't want to rush to judgment on some of these efforts, which we knew were below standard, given what they had been through," he said. "Some of the things here I've been a little more lenient."
That tolerance is about to vanish.
With numerous home practices behind them and an easy travel schedule ahead, Lombardi is ready to cast a critical eye on a team that hasn't scored consistently. He took the Kings' solid performance Saturday in a 3-2 shootout loss to Pittsburgh as a sign that his players have hit their stride and that he can now regularly demand high-caliber efforts. However, he didn't get it Monday in a 4-2 loss at San Jose that extended the team's winless streak to five.
"It's a matter of getting our competitiveness and our emotion where it needs to be," he said. "If we come out and play where we did [Saturday] or give that type of effort, a lot of these other things will fall into place.


text:
Still don't feel good and food as no appeal to me. No pictures today either...LOL
Breakfast: Oatmeal with strawberries..I know it's a cycle 2 food...but it is the closest thing I have to comfort food..and I need some comfort. Green Tea
Lunch: Yogurt Red Grapes and Green Tea
Dinner: Left-over Cauliflower Pizza, Green Tea


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text:
Warlock: Hush My Child / Welcome The Spring: Vocal SATB
To pay and reserve this product click Place On Order and the product will be shipped once back in stock
Warlock: Hush My Child / Welcome The Spring: Vocal SATB
Two SATB arrangements of Pieds En L'Air from Warlock's Capriol, the first being a slumersome lullaby, and the second an optimistic springtime song.
Tomlinson's first arrangement, Hush My Child, was intended to take advantage of Warlock's sumptuous harmonies in the original string orchestra version of Pieds En L'Air, but with voices. This setting was then shown to John Bishop, who responded by creating the text Welcome The Spring to provide a more optimistic and forward-looking interpretation of the same piece.
Both versions are featured in this edition, leaving the choice to the singers and choral leaders themselves!


text:
Clooney relishes 'traitor' attacks
US actor and director George Clooney said this morning he was proud to be denounced as unpatriotic for questioning US policy because he wanted to be on "the right side of history."Of course, this is the side of history that denounces everything that the U.S. and our Coalition partners are doing in Iraq, such as;
Interviewed on BBC television's Newsnight about his latest films Syriana and Good Night, and Good Luck Clooney said that not only did he accept the right to be attacked for his views but he even relished them.
Clooney, who has weathered attacks since opposing the 2003 Iraq invasion, said at one point that it was "frustrating" to be listed as a "traitor" on a set of playing cards, but he also accepted people's right to free speech.
He later admitted he relished the attacks.
"I think it's important to be on the right side of history," Clooney said.
1. Building new water treatment plants in Iraqi villages.And much more, that was just for the month of February and is not a complete list at that.
2. Building and renovating schools.
3. Building and renovating hospitals.
4. Train Iraqi police (although I recognize that liberals do not like police and so would probably not count that as a good thing).
5. Build systems to monitor and control power production and distribution.
Mr. Clooney is proud to be on the side of history that would have Saddam Hussein murdering tens of thousands of people every year, terrorizing and torturing his own population.
Mr. Clooney is proud to be on the side of history that would leave the middle east and Central Asia a cesspit of totalitarian governments ruled by nothing more that the word of a single man, not of law.
Mr. Clooney is proud to be on the side of history were lawless governments support terror. Saddam paid $25,000.00 to the families of terrorists who blew themselves up on city buses, pizzarias, and bar mitzvahs in Tel Aviv and elsewhere in Israel. Mr. Clooney no doubt sees that as the "right side of history".
Why, oh why, are my favorite actors all such political idiots? I love watching Johnny Depp too, but as for his politics, WOW. Ths is very distressing, but I still feel like watching "Secret Window".
And, if you would like to see just what we (by way of the U.S. Army) are doing in Iraq, go here, Defend America.


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Sunday, September 7, 2008
Spotted:!Djimon/Idris /Estelle/Sophie /Adewale
Peep pics of Djimon and his gf Kimora at LAX enroute to NY fashion week about a week ago,the couple at the tennis open a few days later.Estelle was at the pre-Vma party(too bad she wasn't nominated for nething )and Sophie Okenedo (half nigerian ,half jewish) at the premiere of the "Secret Life of bees".And catch edris at the COMECON festival a while back.
Did anyone notice that Estelle is wearing braces?About damn time if you ask me!and I know I always say not-so-nice things about Miss Estelle's choice in clothing but come on,are you serious?Why does she look like she's wearing a night dress?The whole im-wearing-a-headwrap-cuz-i-just -got-out-of-bed-and-am having-a-bad-hair-day-cuz-my-stylist-isn't-here-yet thing is old.And the vulture purple-to-match-the-nightdress nails are off too!Someone needs to get their act together!
Labels: African Celebs.
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This site does not currently take bookings here on Pitchup.com.
If you are the owner of this site, start taking bookings through Pitchup.com by adding your business details.
Pengarreg is a friendly family-run park on the coast with stunning views over Cardigan Bay surrounded by hills for coastal path walks. Take a break with us and enjoy a relaxing atmosphere.
A warm welcome awaits you from our reception and information desk.
We have a modern toilet block with free hot and cold showers, dishwashing facilities and also a laundry room with washing machines and dryer.
There is also a first class general store on the park which sells all the essentials for your holiday.
The clubhouse is within a short stroll from the caravan park and has a bar, lounge bar, restaurant, entertainment room and outside adventure playground. Children are very welcome.
Our games room is within the club and has pool tables and amusement machines.
On site is a children's safe play area with swings, slide, climbing frame and sandpit. There is also a children's play area outside the club.
Site type
Languages spoken
✓ English
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(2 nights)
Many sites set a maximum occupancy of 6/8 people per pitch, so try breaking your booking down into smaller groups to generate more results. For example, if you're a group of 10, enter 5 people in your initial search and then book 2 pitches.
However, where the pitch or accommodation occupancy allows it, you can make a booking for up to 30 adults and 30 children in one booking.
To book multiple pitches or accommodation, use the 'Special requests' box on the booking page to ask to be sited together. Complete the booking form for the first booking (you can add a password and save your card so that we remember your details). Then click "Make another booking like this" at the top of the confirmation page to make the next booking.
Large groups: check the listing page for any group restrictions set out in the terms and section titled 'Please note'.
Large tents/caravans: check the restrictions on unit dimensions to ensure your unit is suitable for the space you will be provided with.
Leisure on site
Bar or club house
Cycle hire
Evening entertainment
Fitness centre
Games room
Indoor swimming pool
Kids' club
On-site restaurant/cafe
Outdoor swimming pool
Play area
Take away
TV room
Amenities on site
Bath available
Disabled facilities
Drying room
Food shop
Free wifi
Ice pack freezing
Internet access
Parent & baby washroom
Pick-up from public transport
Public telephone
Shower available
Toilet block
Washing-up area
Charging facilities
Chemical disposal
Gas cylinders available
Recycling available
Renewable energy
Touring and motorhomes
Hard standings
Barbecues allowed
Campfires allowed
Commercial vehicles allowed
Dogs allowed
Spectacular scenery
Nearby leisure
Fishing nearby
Golf nearby
Groups welcome
Family friendly
Motorcycle friendly
Rallies welcome
Single-sex groups welcome
Student groups welcome
Nearby amenities
Bar nearby
Public transport nearby
Shop nearby
Pub campsite
Nearest transport
- Coach stations
Aberaeron (Ceredigion): Alban Square Bus Stop
— 6.1 miles
Coach Station
6.1 miles Aberystwyth Bus Station — 8.2 miles
Coach Station
8.2 miles Aberystwyth: University Coach Stop — 8.6 miles
Coach Station
8.6 miles
- Train stations
Aberystwyth Rail Station
— 8.1 miles
Rail Station
8.1 miles Borth Rail Station — 13.6 miles
Rail Station
13.6 miles Aberdovey Rail Station — 17.0 miles
Rail Station
17.0 miles
- Ferry ports
Porth Penrhyn Ferry Landing
— 28.6 miles
Ferry Ports
28.6 miles Barmouth Ferry Landing — 28.9 miles
Ferry Ports
28.9 miles
- Airports
Swansea Airport
— 48.8 miles
48.8 miles
Pengarreg Caravan Park is on the seafront overlooking Cardigan Bay. It is approached nine miles south of Aberystwyth, just off A487 Aberystwyth to Cardigan Road in the village of Llanrhystud, opposite the service station.
Local attractions
The River Wyre which runs adjacent to the caravan park has a mile of private trout and sea trout fishing.
Fishing trips are available from two nearby harbours, but there are plenty of fish to be caught by casting from the beach which is also adjacent to the caravan site. Boats may also be launched from our private boating ramp.
There are pleasant walks on the hills around the parkland. The village of Llanrhystud is half a mile away. It has a post office, service station, public house and a 18-hole golf course.
The university town of Aberystwyth is nine miles to the north with its narrow gauge railway leading to the breathtaking Devil's Bridge Falls.
Six miles south of Llanrhystud is the busy harbour town of Aberaeron. A further ten miles away is the fishing village of New Quay with its golden sandy beaches. Tennis, bowls, swimming baths, pony trekking and many other attractions and activities can be found nearby.
Must see
- Llanerchaeron - National Trust (6.8 miles)
- Vale of Rheidol Railway (Aberystwyth) (7.9 miles)
- Rheilffordd Talyllyn Railway (19.3 miles)
National Trust
- Dolaucothi Gold Mines (20.1 miles)
Cycle routes
Find local routes on the National Cycle Network - over 12,000 miles of cycling routes.


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To the Editor:
I was very happy to read the eye-opening June 26 column, "Failure of appeasement policy toward China aids its military," by A.M. Rosenthal, but I wonder if it ever would open the eyes of the statesmen in the State Department.
To the Editor:
I was very happy to read the eye-opening June 26 column, "Failure of appeasement policy toward China aids its military," by A.M. Rosenthal, but I wonder if it ever would open the eyes of the statesmen in the State Department.
We still remember how in the 1970s, George Bush, the then U.S. ambassador to the United Nations, had a tough time convincing the polity of nations that the United States could not agree to permit Mao Tse Tung's Communist People's Republic of China, known for her poor human rights record, to join the elite world class club, known as the United Nations and leave a long-time faithful friend, Chiang Kai Shek's Republic of China in the lurch.
And then, on the ill-conceived advice of the Nixon-Kissinger duo, the same George Bush made a somersault within a short span of time to tell the same United Nations that the United States welcomed the entry of the People's Republic not only to become the member of the U.N. but also to occupy the prestigious seat in the Security Council with all the veto powers that go with that privilege.
We have known all along that China's record of human rights has been shoddy. In very recent years, we saw the Tiananmen incidents, when the Communists had dared the world, which kept watching it silently. She has provided the forbidden nuclear weaponry and other military aid to Pakistan, to Saddam Hussein of Iraq, and to the Ayatollahs of Iran. China bedecked her own hat by putting a few new feathers in it for its success in extracting one trade concession after another from Bill Clinton's administration since 1993.
How long would the pundits in our State Department continue to enjoy the luxury of self-deceptions? Will they ever perceive these prescient warnings? I wonder!
For some very odd reasons, on the contrary, the Clinton administration has been reluctant to recognize the friendship of peace-loving India, a continent that has begun to awaken and show that it has that very potential which had attracted the world to her shores since time immemorial for her fine culture, polite people, immense wealth, and a tremendous market of over 700 million middle-class buyers for anything and everything.


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Reward is one of the important factor to attract or retain the current customers.For hotlink,there are rewards for the users as well especially those who use for many years.
Other than birthday of the users,the users also can get surprises for the anniversary of the day they signed up.Other than that,there is weekly special as well for the users,for instance there can buy the games at a very low price than normal day.
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Here it is in pictures. It's really not an exact science.
Start with tomatoes, garlic, onions and olive oil. Roast the whole lot, blend and freeze.
(or can if you can. :)
I can't claim these were my garden tomatoes unfortunately. Mine are ripening in a nice gradual way which means I get to enjoy some every day but not in large quantities.
Garlic that my brother grew. I'm so proud.
Drizzle in olive oil and wrap in tin foil. Bake.
Drizzle in olive oil and wrap in tin foil. Bake.
I roasted them at 400 for about 1 hour. It smelled amazing.
Mmm... roasted garlic. A whole new world has just opened up.
This stuff is going to be great on spaghetti, in chili, lasagna... Mmmm.
Like how Sophie's toy photobombed that one?


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Oedipus classic tragedy
Oedipus Rex has long been included in the library which all students in the West must read, at some point, to understand the foundations of literature and the roots of Western Civilization. It embodies much of what scholars consider the crucial elements of classical tragedy, and forces its readers or audience to deeply consider the literary fabric of whatmakes tragic protagonist. In it, Oedipus must face his tragic flaw, eventually come to a terrible realization, and become forever immortalized in Western Literature. This paper aims to discuss the basic element of classical plot and discuss Oedipus' role as a tragic protagonist, the character at the center of Greek tragedy.
Aristotle distinguished plot as one of the most important elementscritical to distinguish a classic tragedy. Oedipus is a tragedy in classical style plot with exposition, rising action, and climax. Its plot takes the path of tragedy as Oedipus' fate reverses so he must recognize the horrible truth, and finally experiences great suffering. The plot starts with the exposition of the dramatic conflict which is when no one wants to render any information to Oedipus aboutLaius's murderer and he struggles to get Teiresias the messenger and the shepherd to talk when he desperately wanted to solve the mystery but he keeps being urged to drop it. The plot then follows with the rising action. The climax then brings a turning point, or reversal, at the high point of action when Oedipus realizes he has slept with his mother and killed his father. In this moment ofhorror is when he understands what he has done which makes this part of the play the psychological and emotional climax of the play. The falling action then occurs and the tragedy ends with the catastrophe.
The plot of Sophocles' Oedipus Rex follows the general model of tragedy set forth by Aristotle, telling the tale of good fortune changing to bad, as a character of highborn origin, good nature, andenviable prosperity falls into calamitous ends. Oedipus came from a noble family, was very wealthy, had children, and was looked up to by many people. He was renowned for his intelligence and his capacity to solve riddles, by which he became king of Thebes after solving the riddle of the Sphinx, a supernatural being that had held the city captive. However, Oedipus' fortune takes a terrible turnat the end of the play. His story ends in catastrophe as his character has to be enlightened with new knowledge of the truth about the horrid prophecies that prescribed his own horrid acts. Furthermore, he realizes his own flaw and confronts his wrongdoings so deeply that he decides to punish himself. While the audience watches Oedipus' fall from prosperity alongside the revelation of his trueidentity and the fact that no one could really side step his or her destiny. Indeed, the importance of plot in classical tragedy was tied into theater's role in ancient Greek society. Theater was not something that was created merely for entertainment purposes, but instead strategically promoted the cultural values, and more specifically, the religious beliefs that ruled Greek life. One of thesebeliefs was that the destiny of each individual was decided upon by the fates, which decided the good or evil attributes of a person's nature, what will happen in his or her lifetime, and when that lifetime will come to an end. This was something to be considered while watching Oedipus vainly try to disregard the increasingly obvious truth.
Classical tragedies spotlight the catastrophic and patheticfall of a tragic protagonist, the traits of which can easily be applied to King Oedipus. Such an individual is neither a villain, nor model of perfection. Essentially, a tragic protagonist possesses decency and acts out of good intentions – a good, but not perfect person, who falls from prosperity to misfortune through his own tragic flaw or harmatia. Indeed, Oedipus has a fatal flaw, his pride,...
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Transmission-blocking vaccines (TBVs) are considered an integral element of malaria eradication efforts. Despite promising evaluations of Plasmodium falciparum Pfs25-based TBVs in mice, clinical trials have failed to induce robust and long-lived Ab titers, in part due to the poorly immunogenic nature of Pfs25. Using nonhuman primates, we demonstrate that multiple aspects of Pfs25 immunity were enhanced by antigen encapsulation in poly(lactic-co-glycolic acid)–based [(PLGA)-based] synthetic vaccine particles (SVP[Pfs25]) and potent TLR-based adjuvants. SVP[Pfs25] increased Ab titers, Pfs25-specific plasmablasts, circulating memory B cells, and plasma cells in the bone marrow when benchmarked against the clinically tested multimeric form Pfs25-EPA given with GLA-LSQ. SVP[Pfs25] also induced the first reported Pfs25-specific circulating Th1 and Tfh cells to our knowledge. Multivariate correlative analysis indicated several mechanisms for the improved Ab responses. While Pfs25-specific B cells were responsible for increasing Ab titers, T cell responses stimulated increased Ab avidity. The innate immune activation differentially stimulated by the adjuvants revealed a strong correlation between type I IFN polarization, induced by R848 and CpG, and increased Ab half-life and longevity. Collectively, the data identify ways to improve vaccine-induced immunity to poorly immunogenic proteins, both by the choice of antigen and adjuvant formulation, and highlight underlying immunological mechanisms.
Elizabeth A. Thompson, Sebastian Ols, Kazutoyo Miura, Kelly Rausch, David L. Narum, Mats Spångberg, Michal Juraska, Ulrike Wille-Reece, Amy Weiner, Randall F. Howard, Carole A. Long, Patrick E. Duffy, Lloyd Johnston, Conlin P. O'Neil, Karin Loré
Allogeneic stem cell transplantation (allo-SCT) can cure some patients with hematopoietic malignancy, but this relies on the development of a donor T cell alloreactive immune response. T cell activity in the first 2 weeks after allo-SCT is crucial in determining outcome, despite the clinical effects of the early alloreactive immune response often not appearing until later. However, the effect of the allogeneic environment on T cells is difficult to study at this time point due to the effects of profound lymphopenia. We approached this problem by comparing T cells at week 2 after allograft to T cells from autograft patients. Allograft T cells were present in small numbers but displayed intense proliferation with spontaneous cytokine production. Oligoclonal expansions at week 2 came to represent a substantial fraction of the established T cell pool and were recruited into tissues affected by graft-versus-host disease. Transcriptional analysis uncovered a range of potential targets for immune manipulation, including OX40L, TWEAK, and CD70. These findings reveal that recognition of alloantigen drives naive T cells toward a unique phenotype. Moreover, they demonstrate that early clonal T cell responses are recruited to sites of subsequent tissue damage and provide a range of targets for potential therapeutic immunomodulation.
Charlotte F. Inman, Suzy A. Eldershaw, Joanne E. Croudace, Nathaniel J. Davies, Archana Sharma-Oates, Tanuja Rai, Hayden Pearce, Mirjana Sirovica, Y.L. Tracey Chan, Kriti Verma, Jianmin Zuo, Sandeep Nagra, Francesca Kinsella, Jane Nunnick, Rasoul Amel-Kashipaz, Charles Craddock, Ram Malladi, Paul Moss
Myeloid leukocytes are essentially involved in both tumor progression and control. We show that neo-adjuvant treatment of mice with an inhibitor of CSF1 receptor (CSF1R), a drug that is used to deplete tumor-associated macrophages, unexpectedly promoted metastasis. CSF1R blockade indirectly diminished the number of NK cells due to a paucity of myeloid cells that provide the survival factor IL-15 to NK cells. Reduction of the number of NK cells resulted in increased seeding of metastatic tumor cells to the lungs but did not impact on progression of established metastases. Supplementation of mice treated with CSF1R-inhibitor with IL-15 restored numbers of NK cells and diminished metastasis. Our data suggest that CSF1R blockade should be combined with administration of IL-15 to reduce the risk of metastasis.
Michal Beffinger, Paulino Tallón de Lara, Sònia Tugues, Marijne Vermeer, Yannick Montagnolo, Isabel Ohs, Virginia Cecconi, Giulia Lucchiari, Aron Gagliardi, Nikola Misljencevic, James Sutton, Roman Spörri, Burkhard Becher, Anurag Gupta, Maries van den Broek
The excessive production of type I IFNs is a hallmark and a main pathogenic mechanism of many autoimmune diseases, including systemic lupus erythematosus (SLE). In these pathologies, the sustained secretion of type I IFNs is dependent on the improper activation of plasmacytoid DCs (pDCs) by self–nucleic acids. However, the nature and origin of pDC-activating self–nucleic acids is still incompletely characterized. Here, we report that exosomes isolated from the plasma of SLE patients can activate the secretion of IFN-α by human blood pDCs in vitro. This activation requires endosomal acidification and is recapitulated by microRNAs isolated from exosomes, suggesting that exosome-delivered microRNAs act as self-ligands of innate single-stranded endosomal RNA sensors. By using synthetic microRNAs, we identified an IFN induction motif that is responsible for the TLR7-dependent activation, maturation, and survival of human pDCs. These findings identify exosome-delivered microRNAs as potentially novel TLR7 endogenous ligands able to induce pDC activation in SLE patients. Therefore, microRNAs may represent novel pathogenic mediators in the onset of autoimmune reactions and potential therapeutic targets in the treatment of type I IFN–mediated diseases.
Valentina Salvi, Veronica Gianello, Sara Busatto, Paolo Bergese, Laura Andreoli, Ugo D'Oro, Alessandra Zingoni, Angela Tincani, Silvano Sozzani, Daniela Bosisio
Chimeric antigen receptor–modified (CAR-modified) T cells have shown promising therapeutic effects for hematological malignancies, yet limited and inconsistent efficacy against solid tumors. The refinement of CAR therapy requires an understanding of the optimal characteristics of the cellular products, including the appropriate composition of CD4+ and CD8+ subsets. Here, we investigated the differential antitumor effect of CD4+ and CD8+ CAR T cells targeting glioblastoma-associated (GBM-associated) antigen IL-13 receptor α2 (IL13Rα2). Upon stimulation with IL13Rα2+ GBM cells, the CD8+ CAR T cells exhibited robust short-term effector function but became rapidly exhausted. By comparison, the CD4+ CAR T cells persisted after tumor challenge and sustained their effector potency. Mixing with CD4+ CAR T cells failed to ameliorate the effector dysfunction of CD8+ CAR T cells, while surprisingly, CD4+ CAR T cell effector potency was impaired when coapplied with CD8+ T cells. In orthotopic GBM models, CD4+ outperformed CD8+ CAR T cells, especially for long-term antitumor response. Further, maintenance of the CD4+ subset was positively correlated with the recursive killing ability of CAR T cell products derived from GBM patients. These findings identify CD4+ CAR T cells as a highly potent and clinically important T cell subset for effective CAR therapy.
Dongrui Wang, Brenda Aguilar, Renate Starr, Darya Alizadeh, Alfonso Brito, Aniee Sarkissian, Julie R. Ostberg, Stephen J. Forman, Christine E. Brown
Studies in human peripheral blood monocyte–derived macrophages in vitro have shown clear evidence that multiple macrophage polarization states exist. The extent to which different alveolar macrophage (AM) polarization states exist in homeostasis or in the setting of severe injury such as acute respiratory distress syndrome (ARDS) is largely unknown. We applied single-cell cytometry TOF (CyTOF) to simultaneously measure 36 cell-surface markers on CD45+ cells present in bronchoalveolar lavage from healthy volunteers, as well as mechanically ventilated subjects with and without ARDS. Visualization of the high-dimensional data with the t-distributed stochastic neighbor embedding algorithm demonstrated wide diversity of cell-surface marker profiles among CD33+CD71+CD163+ AMs. We then used a κ-nearest neighbor density estimation algorithm to statistically identify distinct alveolar myeloid subtypes, and we discerned 3 AM subtypes defined by CD169 and PD-L1 surface expression. The percentage of AMs that were classified into one of the 3 AM subtypes was significantly different between healthy and mechanically ventilated subjects. In an independent cohort of subjects with ARDS, PD-L1 gene expression and PD-L1/PD-1 pathway–associated gene sets were significantly decreased in AMs from patients who experienced prolonged mechanical ventilation or death. Unsupervised CyTOF analysis of alveolar leukocytes from human subjects has potential to identify expected and potentially novel myeloid populations that may be linked with clinical outcomes.
Eric D. Morrell, Alice Wiedeman, S. Alice Long, Sina A. Gharib, T. Eoin West, Shawn J. Skerrett, Mark M. Wurfel, Carmen Mikacenic
The underlying pathology of atopic dermatitis (AD) includes impaired skin barrier function, susceptibility to Staphylococcus aureus skin infection, immune dysregulation, and cutaneous dysbiosis. Our recent investigation into the potential role of Gram-negative skin bacteria in AD revealed that isolates of one particular commensal, Roseomonas mucosa, collected from healthy volunteers (HVs) improved outcomes in mouse and cell culture models of AD. In contrast, isolates of R. mucosa from patients with AD worsened outcomes in these models. These preclinical results suggested that interventions targeting the microbiome could provide therapeutic benefit for patients with AD. As a first test of this hypothesis in humans, 10 adult and 5 pediatric patients were enrolled in an open-label phase I/II safety and activity trial (the Beginning Assessment of Cutaneous Treatment Efficacy for Roseomonas in Atopic Dermatitis trial; BACTERiAD I/II). Treatment with R. mucosa was associated with significant decreases in measures of disease severity, topical steroid requirement, and S. aureus burden. There were no adverse events or treatment complications. We additionally evaluated differentiating bacterial metabolites and topical exposures that may contribute to the skin dysbiosis associated with AD and/or influence future microbiome-based treatments. These early results support continued evaluation of R. mucosa therapy with a placebo-controlled trial.
Ian A. Myles, Noah J. Earland, Erik D. Anderson, Ian N. Moore, Mark D. Kieh, Kelli W. Williams, Arhum Saleem, Natalia M. Fontecilla, Pamela A. Welch, Dirk A. Darnell, Lisa A. Barnhart, Ashleigh A. Sun, Gulbu Uzel, Sandip K. Datta
Kidney injury is a frequent outcome in patients with disseminated Candida albicans fungal infections. IL-17 receptor (IL-17R) signaling is critical for renal protection against disseminated candidiasis, but the identity and function of IL-17–responsive cells in mediating renal defense remains an active area of debate. Using BM chimeras, we found that IL-17R signaling is required only in nonhematopoietic cells for immunity to systemic C. albicans infection. Since renal tubular epithelial cells (RTEC) are highly responsive to IL-17 in vitro, we hypothesized that RTEC might be the dominant target of IL-17 activity in the infected kidney. We generated mice with a conditional deletion of IL-17 receptor A (Il17ra) in RTEC (Il17raΔRTEC). Strikingly, Il17raΔRTEC mice showed enhanced kidney damage and early mortality following systemic infection, very similar to Il17ra–/– animals. Increased susceptibility to candidiasis in Il17raΔRTEC mice was associated with diminished activation of the renal protective Kallikrein-kinin system (KKS), resulting in reduced apoptosis of kidney-resident cells during hyphal invasion. Moreover, protection was restored by treatment with bradykinin, the major end-product of KKS activation, which was mediated dominantly via bradykinin receptor b1. These data show that IL-17R signaling in RTEC is necessary and likely sufficient for IL-17–mediated renal defense against fatal systemic C. albicans infection.
Kritika Ramani, Chetan V. Jawale, Akash H. Verma, Bianca M. Coleman, Jay K. Kolls, Partha S. Biswas
Although immune checkpoint inhibitors have resulted in durable clinical benefits in a subset of patients with advanced cancer, some patients who did not respond to initial anti–PD-1 therapy have been found to benefit from the addition of salvage chemotherapy. However, the mechanism responsible for the successful chemoimmunotherapy is not completely understood. Here we show that a subset of circulating CD8+ T cells expressing the chemokine receptor CX3CR1 are able to withstand the toxicity of chemotherapy and are increased in patients with metastatic melanoma who responded to chemoimmunotherapy (paclitaxel and carboplatin plus PD-1 blockade). These CX3CR1+CD8+ T cells have effector memory phenotypes and the ability to efflux chemotherapy drugs via the ABCB1 transporter. In line with clinical observation, our preclinical models identified an optimal sequencing of chemoimmunotherapy that resulted in an increase of CX3CR1+CD8+ T cells. Taken together, we found a subset of PD-1 therapy–responsive CD8+ T cells that were capable of withstanding chemotherapy and executing tumor rejection with their unique abilities of drug efflux (ABCB1), cytolytic activity (granzyme B and perforin), and migration to and retention (CX3CR1 and CD11a) at tumor sites. Future strategies to monitor and increase the frequency of CX3CR1+CD8+ T cells may help to design effective chemoimmunotherapy to overcome cancer resistance to immune checkpoint blockade therapy.
Yiyi Yan, Siyu Cao, Xin Liu, Susan M. Harrington, Wendy E. Bindeman, Alex A. Adjei, Jin Sung Jang, Jin Jen, Ying Li, Pritha Chanana, Aaron S. Mansfield, Sean S. Park, Svetomir N. Markovic, Roxana S. Dronca, Haidong Dong
Malaria remains one of the world's most significant human infectious diseases and cerebral malaria (CM) is its most deadly complication. CM pathogenesis remains incompletely understood, hindering the development of therapeutics to prevent this lethal complication. Elevated levels of the chemokine CXCL10 are a biomarker for CM, and CXCL10 and its receptor CXCR3 are required for experimental CM (ECM) in mice, but their role has remained unclear. Using multiphoton intravital microscopy, CXCR3 receptor– and ligand–deficient mice and bone marrow chimeric mice, we demonstrate a key role for endothelial cell–produced CXCL10 in inducing the firm adhesion of T cells and preventing their cell detachment from the brain vasculature. Using a CXCL9 and CXCL10 dual-CXCR3-ligand reporter mouse, we found that CXCL10 was strongly induced in the brain endothelium as early as 4 days after infection, while CXCL9 and CXCL10 expression was found in inflammatory monocytes and monocyte-derived DCs within the blood vasculature on day 8. The induction of both CXCL9 and CXCL10 was completely dependent on IFN-γ receptor signaling. These data demonstrate that IFN-γ–induced, endothelium-derived CXCL10 plays a critical role in mediating the T cell–endothelial cell adhesive events that initiate the inflammatory cascade that injures the endothelium and induces the development of ECM.
Elizabeth W. Sorensen, Jeffrey Lian, Aleksandra J. Ozga, Yoshishige Miyabe, Sophina W. Ji, Shannon K. Bromley, Thorsten R. Mempel, Andrew D. Luster
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