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The column doesn´t really make the point the headline states. Not many voters or potential voters are tying Rand Paul to much of anything Barack Obama does right now. I´ve got my own reservations about Rand Paul, but I don´t see how the Bergdahl swap applies, for good or bad.
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Phillip Klein is reaching. Not just the right is upset about the release of five top terrorists. Not just the right thought Obama´s speech at West Point was pathetic. There was consensus on both of these events across the board, except for the looney left. The disgust with Obama is broad. Mr Klein needs to quit trying to divide our country on this.I agree that few are thinking about Rand Paul at this time, all the focus is on the traitor sitting in the Oval Office.
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#1, I agree that the column fails to make its case. It makes the claim that Obama´s failed foreign policy is bad for Rand Paul because Rand Paul is, more or less, an isolationist (although his position is much more complex than that word implies). Yet it fails to point out any way in which Rand Paul´s "isolationism" would lead to similar results to the foreign policy pursued by Obama.
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The Bowe Bergdahl furor is NOT actually bad news for Rand Paul, Ron Paul, or even Mrs. Paul.A silly article.
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Merely an attack ad against Paul with little substance to back up the headline and accusation.
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The world is no longer "Free vs Communist." It´s more complex, and more dangerous than ever once the "Axis of Evil" goes nuclear. For two decades since the demise of the USSR the USA has floundered in its foreign policy. There is no national interest at stake to this open borders/NAFTA-ized free trade nation we´ve become. We´re the tailgater who suddenly finds himself at the head of a pack of cars, the only "superpower" standing. What we have become is largely a mercenary for the Saudis and oil sheiks, like Qatar and Kuwait. We´ve been NATO for the most part since 1992, bungling in the Balkans and the Horn of Africa, North Africa and Syria. Until a national (consensus, bi-partisan) interest is developed and put at the core of our foreign policy, it won´t matter who is President or Secretary of State. We´ll continue bumbling as #1 until China decides to take the role for real, but that won´t be until its hegemony in Pacific Asia is complete.
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Philanthropist Eli Broad (L) and his wife Edythe Broad attend the American Friends of the Israel Philharmonic Orchestra event in Beverly Hills, California July 16, 2014. REUTERS/Phil McCarten (UNITED STATES - Tags: ENTERTAINMENT BUSINESS)
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Screen sighs: why 16:9 shouldn't always be the way
The Guardian criticises the iPad Air 2's display, due to Apple using what the reviewer refers to in the verdict as a "square screen". Of course, the screen isn't actually square, but it's squarer than the bulk of those used by its rivals. Apple, since the original iPad, has provided a tablet with a 4:3 aspect ratio, somewhat aping the printed page. By contrast, most competing tablets have primarily been designed for landscape orientation, in 16:9, common for movies.
If nothing else, this showcases assumptions regarding intentions for the devices themselves. Android tablets have been more geared towards movie and TV consumption, whereas iPads 'compromised' that use-case in order to provide a device with wider scope. I explore this further in a piece for Stuff, which examines Google's new Nexus displays, the tablet now following Apple's lead.
The short of that is about versatility. 16:9 leaves little room in landscape for content when using the virtual keyboard; in portrait it's often unsatisfying for reading, because the viewport is so narrow. (Oddly, the Guardian reviewer calls out the iPad for having black bars at the side of comic books, despite those blank spaces being perfectly good for placing your thumbs and flipping pages, without covering content; by contrast, tablets closer to 9:16 aspect ratios in portrait may have black bars at the top and bottom, which the reviewer had a go at the iPad for regarding video.)
Of course, the best aspect ratio for you depends entirely on what you're doing with a device, and if you only want TV on the go, then having a device with a screen ratio similar to a telly's makes sense; however, if you want a device suitable for a much wider range of tasks, 16:9 isn't the smartest move, something Apple knew all along, something Google's now embracing, and something Microsoft's also figured out with its new Surface Pro tablets, which use a 3:2 aspect.


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Automating the complex tasks of user provisioning is a goal of many IT organizations. When new employees get the right accounts, groups, mail, and application access right on day one, they're immediately able to start work and provide benefit to the company.
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Acquisitions - Enstratius, RemoteScan, StatSoft


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Enter by December 20th!
With 2014 fast approaching, it's time to reflect on the past year and celebrate your accomplishments.
What did you achieve in 2013? Use that incredible momentum to look ahead into the next 365 days to go after new goals with gusto.
Win a fitbook, a personal 12-week fitness & nutrition journal!
Fitbook is a journal that's great for setting a 12-week goal — like something you want to achieve in late Spring or early Summer of 2014 — while also helping you achieve smaller goals on a weekly basis. These small weekly goals will help you reach your one big goal. Along the way, you can use fitbook to track progress by recording your workouts and runs. Also log your food intake so you can better understand how your nutrition can help you be the best runner and athlete you can be.
Creator of fitbook, Angela Manzanares is on a mission to inspire people to live life fit. Her company, fitlosophy creates these 12-week journals to help people lose weight, get healthy, or achieve a fitness goal.
Writing down your goals, according to research, is the key to reaching them. In one of the largest weight-loss studies to date, Kaiser Permanente asked nearly 1700 participants to eat healthy and exercise. Nearly 2/3 of participants lost 9 lbs over the 6-month period; however, those who used a diet tracker and fitness journal lost an average of 20 lbs – more than double the amount of the non-journalers.
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HIV Transmission Deep Kissing
Here's a taste of what TheBody.com has to offer on this topic:
Ask the Experts
Deep Kissing and HIV TransmissionHello,I just read this article which quotes Luc Montaigner:=============Deep kissing and HIV transmissionContrary to some studies, renowned French researcher and scientist, Prof. Luc Montaigner, who discovered that AIDS is caused by the Human...
Response from Ryan M. Kull, C.S.W
Columbia University's Health & Related ServicesThanks for the update. I must have blinked too, because Luc Montaigner's announcement is news to me. I have not been able to find anymore specific information about his statement. I am so wary of the press when it comes to relaying... Read more »
Scared about kissing and what is prolonged deep kissing?Please help me. I am sexually inactive but go to strip clubs often. I do not have much... Read more »
Deep kissing can cause HIV?I was 9 years old. I had a deep kissing with my cousins everyday. I forgot, at that time we had a... Read more »
A Kiss Is Just a KissIf you were anywhere near a television set last summer, you inevitably heard about that case of HIV infection that appears to have resulted from kissing and kissing alone. And, admit it -- the news gave you at least a moment's pause. You couldn't... Read more »
HIV i-Base/Treatment Action Group 2012 Pipeline Report Reveals Deep Gaps Between Scientific Promise and Program DeliveryWashington, D.C. -- On the eve of the XIX International AIDS Conference in Washington, D.C., a new report by HIV i-Base (U.K.) and Treatment Action Group (TAG) (U.S.) reveals the deepening gulf between new scientific advances that make it possible... Read more »
Prevalence of Childhood Sexual Abuse and Physical Trauma in an HIV-Positive Sample From the Deep SouthSexual and severe physical abuse in childhood is associated with the following in adults: post-traumatic stress disorder, anxiety, depression, dissociation, substance abuse, revictimization, high-risk sexual behaviors, and engaging in abuse of... Read more »
HIV TransmissionTable of Contents How HIV Spreads Methods of Transmission Rare Types of Transmission Avoiding Transmission How HIV Spreads Many people still do not understand how HIV is passed, or transmitted, fromone person to another. Knowing the... Read more »
Connect With Others
Posted by Katietaylor, 1 ReplyPlease can someone give me their honest opinion on whether this is a reason for me to be concerned and tested?
Im going out of my mind with worry and keep checking my body for HIV symptoms due what I believe my risky exposure.
Im a 34 year old woman... Read more »
HIV from deep kissing?
Posted by caman1313I engaged in open mouth kissing with a girl at a bar that I didn't know very well. My gums bleed when I brush and I'm worried about potential infection. I kissed the girl maybe 5 times throughout the night. The next morning I woke up paranoid I... Read more »
Deep Kissing
Posted by Anonymous, 2 RepliesI dont realy know how to explain, ive been deep kissing a girl in advanced hiv status, since that exposure that someone said theres now risk i have been with candidiasis, angular cheilitis, pains in the gums, all my life as ended, or almost ended, i... Read more »
Deep Kissing & Oral Sex Risk Comparison
Posted by supernervousguy, 1 ReplyI know this is probably an obnoxious question, but hopefully someone can help satisfy my curiosity. I am aware that deep/french/tongue kissing is next to zero risk for transmission. However, in many places online and on this forum, it is placed in... Read more »
Guides for People With HIV


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CAPE CORAL, Fla.-CAPE CORAL, Fla. -- Another round of storms means another round of clean up in Cape Coral's canals. Crews are removing debris build-up from grates. They started Wednesday morning at a canal on Viscaya Parkway and Southeast 20th Court.
While some grates are checked multiple times a day, crews are checking all of them, which is over a dozen, to prevent flooding.
Hanging over the edge of the canals and picking up debris with a special stick, a Cape Coral public works crew is on a mission. "We have to release all the horticulture debris, garbage, pick the garbage out," said Vinnie Morelli, with Cape Coral Public Works.
The canals are set on a tiered system and some are stocked with sterile carp. The fish are designed to eat specific kinds of grass inside.
But while the grates trap the carp, they also trap the grass,coconuts, large sticks, and trash. They can also trap other creatures like a turtle crews rescued on Tuesday.
After heavy storms and rain, the grass can build up into a sticky swamp and cause flooding. "You'll end up with dead fish, smells really bad. Water will back up and raise the level in the system," said Morelli.
It's happening outside Mercedes Baldeon's home. "We called the city for this one because this is not good for the house, my dog, for everybody," she said.
She's happy to know crews are taking care of the problem. "When they clean, it's good because now it's clean today, the water," she said.
The city is also monitoring weirs in the canals. A weir acts as a small dam to regulate water levels. Right now, all the weirs in canals are as low as they can go in hopes of preventing flooding.


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Chinese news outlet Huanqiu has today quoted nameless sources from the South Korean military as stating that intelligence confirms a long range rocket will be launched by North Korea between December and January. The news follows a torrent of speculation surrounding satellite imagery released by DigitalGlobe which allegedly reveal increased activity at North Korea's West
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text: 705 N Chicago Ave Status: Off Market MLS#: 1278346 Contact Email this listing Calculate Mortgage Print Flyer Get Directions Request a Showing Off Market 705 Chicago Ave, South Milwaukee, WI 53172 is no longer on the market or has been removed from the MLS. Similar to 705 Chicago Ave: Ask an Agent About 705 Chicago Ave * Required fields Send Your Question × Monthly Payment Estimator Price: Down Payment: % Loan Amount: Loan Type: 30 Year Fixed 15 Year Fixed 5/1 ARM Interest Rate: % Est. Tax & Insurance: % ($/mo.) Est. Monthly Payment: $478 per month × Email a Listing 705 Chicago Ave, South Milwaukee WI, 53172 From: Name: Email: To: Name: Email: Subject: Message: Take a look at this property I found on MilwaukeeRealEstateSearch.com: http://www.milwaukeerealestatesearch.com/homes/705-N-Chicago-Ave/South-Milwaukee/WI/53172/25926768/ Send a copy of this message to me Send Email


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Resources for Faculty
We invite you to browse our faculty resources pages to learn how you can best assist students with disabilities. We hope this information will aid you in understanding the needs of students and provide you with information about services, policies, and procedures. This page will continue to evolve, and we welcome any input or suggestions that will help us enhance its effectiveness and value for the CC faculty.
We extend our sincere appreciation for all you do to provide accommodations and support to our students with disabilities so they are able to make the most of their academic experiences at CC. You are always welcome to contact Accessibility Resources if you need additional information or have questions or concerns.
Jan Edwards
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Stryper Coach House 8/15/13 "It's mind boggling that we've been around for 30 years," said Stryper front man Michael Sweet to a crowd of several hundred fans at the Coach House in San Juan Capistrano, during an intimate all acoustic performance with his band mate, guitarist Oz Fox. The guitar duo st ... More >>
Jenna Haze, Aurora Snow, Dani Daniels and more of the 20 greatest adult film actors and actresses in OC history
Updated at end, with resignation ORIGINAL POST JUNE 4 2:00 P.M.: Ingrid Valdez consulted Newport Beach dentist Dr. Sherri Lee Worth in 2009 hoping Worth would change Valdez's "gummy smile," a fractured tooth and her discolored front teeth. Dr. Worth's website showed her work with celebrities li ... More >>
Ingrid Valdez consulted Newport Beach dentist Dr. Sherri Lee Worth in 2009 hoping Worth would change Valdez's "gummy smile," a fractured tooth and her discolored front teeth. Dr. Worth's website showed her work with celebrities like Motley Crüe drummer Tommy Lee, American Idol singer Ace Young, and ... More >>
[Summer Guide 2012] The perfect aural schedule for your OC summer
I grew up in a town where almost every kid wore a jean jacket and worshiped at the altar of Ozzy Osbourne. KNAC blared from garages and Skid Row was played over the loudspeaker at our city's annual carnival. Needless to say, I know a thing or two about metal, which might have something to do with ... More >>
Alex Kirst, former member of seminal LA glam rockers The Nymphs and, later, longtime drummer for Iggy Pop's band, died tragically Jan. 13. According to The Desert Sun, Kirst was killed in a hit-and-run accident in Cathedral City, Riverside County. The Nymphs had their heyday in the late '80s and ... More >>
photo by Photography by Chad SengstockIf you were dying to watch the Jonas Brothers, go to the Ozzfest and watch Dahga Bloom at the House of Blues but didn't have the cash, you're in luck. For today only, you can buy select Live Nation tickets to various Verizon Wireless Amphitheater and House of ... More >>
Jack's Mannequin front man talks candidly about his cancer, remains cagey about how long the reunion of his old band will last
Andrew YoussefLive at the House of Blues Anaheim Last Night: Thrice at the House of Blues Anaheim (11/25/09)Better Than: Going to Warped Tour or Bamboozle Left just to see Thrice.My first Thrice show was back in 2002 at the House of Blues Anaheim when they opened for Face To Face. I had no idea w ... More >>
Sending up the biopic, Walk Hard sells cheap laughs, lame cameos and lifeless Cox
FEEDBACK: Goth-Metal Clown Fifi Larue's Advice Can Help You Attain It
The Family That Twists Nobs Together: California Sound Studios has the Wright staff
Costa Mesa-based band Supernova is taking on the Motley Crue drummer, reality TV God Mark Burnett and the CBS network over the band on Rock Star Supernova performing under just the name Supernova: Rock band seeks to stop CBS and Mark Burnett's new band from performing under the name Supernova Requ ... More >>
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The rock & roll tragedies that should have been
And sexy! The Catheters!
The Big Time Blues Fest is back
Suddenly famous, the guys in Lit figure out how to mix high-octane success with being as nice as they ever were


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Rebounding from a movie that pissed off and confused America, the actor gives one of his best performances in Spike Jonze's Her
Mexicans pay in blood for America's War on Drugs
Noah Baumbach goes west for his latest self-obsessed, unlikable protagonist in 'Greenberg'
Alpha Dog, Borat, Casino Royale
At home with Penelope Cruz
Alejandro Amenabars The Sea Inside
Medea Project neuters, cooks, eats itself!
Touching the Void is a taut, gripping cliff-hanger!!!
How Model Quality Introductions will outsource your dating life. If youre rich
None to be had in Finchers Panic Room


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Sensors 2011, 11(12), 11736-11751; doi:10.3390/s111211736
Published: 16 December 2011
Abstract: Semiconductor quantum dots (QDs) are nanometre-scale crystals, which have unique photophysical properties, such as size-dependent optical properties, high fluorescence quantum yields, and excellent stability against photobleaching. These properties enable QDs as the promising optical labels for the biological applications, such as multiplexed analysis of immunocomplexes or DNA hybridization processes, cell sorting and tracing, in vivo imaging and diagnostics in biomedicine. Meanwhile, QDs can be used as labels for the electrochemical detection of DNA or proteins. This article reviews the synthesis and toxicity of QDs and their optical and electrochemical bioanalytical applications. Especially the application of QDs in biomedicine such as delivering, cell targeting and imaging for cancer research, and in vivo photodynamic therapy (PDT) of cancer are briefly discussed.
1. Introduction
Quantum dots (QDs) as colloidal nanocrystalline semiconductors have unique photophysical properties due to quantum confinement effects. They emit different wavelengths over a broad range of the light spectrum from visible to infrared, depending on their sizes and chemical compositions. Compared with the traditional organic fluorophores (e.g., organic dyes and fluorescent proteins), QDs have unique optical and electronic properties, such as larger absorption coefficients, size-tunable light emission, superior signal brightness, resistance to photobleaching and simultaneous excitation of multiple fluorescence colors [1–6]. In addition, the large-surface area of QDs is beneficial to covalently link to biorecognition molecules, such as peptides, antibodies, nucleic acids or small-molecule ligands for further application as fluorescent probes (Figure 1).
These properties of QDs herald a revolution from electronic materials science to biological applications [7]. Current and projected applications of QDs include using fluorescent labels for cellular labeling [1,8,9], intracellular sensors [10,11], deep-tissue and tumor targeting and imaging agents [7,12–17], sensitizers for photodynamic therapy (PDT) [18–21], vectors for gene therapy [22–26], magnetic resonance imaging (MRI) contrast agents [27,28] and so on. This review mainly summarizes the development of synthesis, the surface modification and toxicity of QDs, and briefly focuses on the application developments of QDs in the biomedical field.
2. The Surface Chemistry and Toxicity of QDs
Early in the 1990s, Bawendi and coworkers first reported a synthesis protocol for QDs with highly monodisperse, regular core structure and tunable particle size [29,30]. Up to now, the most successful and well-developed method to prepare highly luminescent II–VI QDs is the TOP/TOPO synthetic approach [31]. However, these QDs are insoluble in water, which limits their biological applications. Therefore, a number of surface functionalization studies have been developed to make QDs water-soluble and biologically compatible [29–37].
In one common approach, the original hydrophobic coatings are replaced by water-soluble functional molecules (e.g., dithiothreitol [38–40], mercaptocarbonic acids [41–44], 2-aminoethanethiol [33,45], dihydrolipoic acid [34–36,46,47], oligomeric phosphines [37,48], peptides [49–57], and cross-linked dendrons [58–61]) through the ligand exchange reactions. Because the optical properties of the inorganic core are often very sensitive to the surface, the ligand exchange process may result in poorer performance, particularly in the case of quantum dots [62].
The second approach is to encapsulate QDs in an amphiphile whose hydrophobic ends interleave with, but do not replace, the organic coating on QDs. This improvement for QDs synthesis is significant: (1) protecting the core/shell structure and maintaining the original photophysics of QDs; (2) making QDs water-soluble; (3) providing a biological interface and multiple functions [7]. However these kinds of QDs are not stable in biological settings because of relativelyweak anchoring of the single and double hydrophobic tails to the particle. Additionally, the hydrophilic end groups of even biocompatible surfactants may not protect nanocrystals from nonspecific biomolecular interactions [31]. Scientists have used amphiphilic polymers instead of simple amphiphile because single polymer chains can contain multiple hydrophobic units, their interactions with the native organic coatings on QDs can be numerous, and thus the encapsulant can be bound more strongly than conventional surfactants. However, the range of amphiphilic polymers for creating stable and nonaggregating QDs in biological settings has been relatively limited. Up to now, most of the amphiphilic polymers used are commercial and their hydrophobic/hydrophilic ratios are fixed, hence the cost is high and it may be different to control the process of forming water-soluble QDs and to optimize the forming conditions [31].
Although QDs have great prospects, the toxicity of QDs cannot be overlooked. During the processing of biological applications (e.g., cancer imaging, targeting and PDT treatment), the degradation products of QDs will do harm to the cells which they contact with, or produce immune responses with the components in blood [17]. The toxic degradation production routes are: first, the oxidation of the nanoparticle core/shell material can cause the release of free cadmium or other heavy metals, which will interrupt the normal cell activities [18]; secondly, the photosensitized production of reactive oxygen intermediates (ROI) also plays an important role in mediating the cell damage [63]; thirdly, the toxicity of capping materials should also be considered, several groups in capping materials such as mercaptoacetic acid and tri-n-octylphosphine oxide (TOPO) could produce toxicity to cells [12].
To reduce the cytotoxicity of QDs, replacement of the cadmium by nontoxic or less-toxic metals such as indium (In), or encapsulation of the core with a biocompatibile shell should be considered. Though In-based semiconducting dots contain arsenic, another toxin, the cytotoxicity of these dots may be small enough to keep the toxicity low. Fisher and coworkers [64] found that QDs could remain within the body for very long periods. Kim [8] reported that larger QDs generally accumulated in the reticuloendothelial system, such as the liver, spleen and lymphatic system for several months, but the size less than 5 nm could be removed by the kidney quickly. So in order to minimize the toxicity of QDs, QDs can be designed as smaller as they can, which can help them more easily to clean them out from the body.
In spite of the fact many investigators have paid close attention to and observed the side-effect of QDs, the definite metabolism of QDs in vivo remains uncertain [65–68]. Thus, it is still a necessary issue to investigate the detailed biochemical and pharmacological mechanism for further application of QDs in the human body.
3. Delivering QDs into Cells
Effective delivery of QDs into the targeted-cell is the primary requirement for the bioapplications of QDs [9,15,17,20,32,54]. It is a major step because if QDs cannot reach their site of action in vivo, they is useless. Furthermore, efficient delivery can also allow a reduction in dosage level, avoid non-specific side effects and reduce toxicity risks [66,69,70]. The current methods for delivering QDs into cells mainly include passive delivery, facilitated delivery and active delivery.
The general passive delivery for QDs is endocytosis, which is simple, without further functionalization of the QDs surface with a targeting ligand for uptake [66]. By incubating with the cells at appropriate concentration and exposure time, QDs will enter into cells though the nonspecific cell endocytosis. However, the nonspecific ingestion of this mode caused ineffective endosomal escape, and would impede the delivery of QDs to the cytoplasm or other organelles. Furthermore, high intracellular concentration of QDs can enhance the cytotoxicity in some cases [69].
Facilitated delivery includes four ways: peptide-mediated uptake, protein-mediated delivery, polymer-mediated delivery and small molecule-mediated delivery [66]. Generally, these molecules are noncovalently assembled onto the surface of QDs for bioconjugation. Facilitated delivery could reduce the nonspecific absorption and side effects. However, QDs could also be uptaken by cell through endocytosis, leading to endosomal sequestration during the facilitated delivery strategies (Figure 2). As is well known, the high acidic of endosomes could degrade the QDs conjugates over time, thus free Polyethyleneimine (PEI) was used to encapsule the QDs conjugates to increase the stability [70]. Considering further application of cell imaging, more general endosomal escape strategies need to be developed in order to expand the application of facilitated delivery.
Active delivery is a direct physical manipulation of the cell by electroporation and microinjection. In comparison to facilitated delivery, QDs conjugates are delivered directly to the cytoplasm via electroporation by an endocytic pathway, without subsequent endosomal escape. However, the high cellular mortality rate and intracellar aggregation occurring during the delivery should be conquered [71]. Compared with electroporation, microinjection could deliver the QDs directly to the cytoplasm with lower cell death rate, and the rate of microinjection of QDs conjugates to cells depends on the physical constraints of cells, including morphology, membrane thickness, height, etc. [66]. Furthermore, this technology is very expensive. Therefore, considering the coexistence of advantages and drawbacks of the mentioned approaches, the appropriate way for delivering QDs into cell should be determined according to the specific experimental requirements. The relationship between the specific examples and the delivery strategies are listed in Table 1 [66].
4. QDs-Based Cancer Targeting and Imaging
The photoluminescence (PL) of QDs is exceptionally bright and stable, making them potential candidates for biomedical imaging and therapeutic interventions. QDs conjugated with cancer specific ligands/antibodies/peptides were found to be effective for detecting and imaging human cancer cells. Gao and coworkers [67] firstly reported the QDs-antibody conjugates for in vivo targeting and imaging cancer, in which QDs-antibody conjugates were used as imaging probe for investigating and tracing QDs-PSMA antibody conjugates in mouse bearing subcutaneous human prostate cancer. It was found that the QDs-antibody conjugates were efficiently and uniformly distributed in prostate tumors due to the specific binding between PSMA antigen in prostate cancer cells and PSMA antibody on QDs. Cai and coworkers [105] conjugated NIR QDs with RED peptide, which could bind to the over-expressed αvβ3 integrin on the surface of U87MG glioblastoma cells and MDA-MB-435 human breast cancer cells to target cancer cell in vivo. By linking QDs to AFP (alpha-fetoprotein) antibody, an important marker for hepatocellular carcinoma cell lines, a specific immunofluorescent probes was obtained for further detection of AFP antibody in human serum. Yu et al. [106] demonstrated that the probe could target the specific hepatocellular carcinoma cells, and the expected results was obtained by investigating distribution of the probes in cancer cells by using a site-by-site measurement. Weng et al. [107] functionalized QDs with anti-HER2 scFv to synthesize the immunoliposome-based nanoparticles (QD-ILs). After incubating with HER2-overexpressing SK-BR-3 and MCF-7/HER2 cells, the QD-ILs exhibited efficient receptor-mediated endocytosis. In vivo fluorescence imaging showed that QD-ILs had localized prominently in tumors as well as in MPS organs (Figure 3). Liu et al. [68] reported a QDs-based wavelength-resolved spectral imaging for molecular mapping of tumor heterogeneity on human prostate cancer tissue specimens. By conjugating different QDs with specific protein biomarkers, such as E-cadherin, high-molecular-weight cytokeratin, p63, and α-methylacyl CoA racemase, structural distinct prostate glands and single cancer cells could be detected and characterized within the complex microenvironments of radical prostatectomy and needle biopsy tissue specimens using the wavelength-resolved spectral imaging.
The main advantage of QDs imaging is that it is non-ionizing and less hazardous [108]. In recent years, several groups have used QD probes for fluorescence immunostaining of fixed cells and tissue specimens [109–113]. QD-based immunohistochemistry (IHC) can improve both diagnostic sensitivity and specificity. In addition, because multiplexed QD staining can be carried out on intact cells and tissue specimens, it is expected to provide correlated molecular and morphological information, at the same time, this type of integrated biomarker and morphological data are not available from traditional analytical methods such as mass spectrometry, gene chips, protein microarrays, and polymerase chain reactions [109]. However, medical applications of QD-based IHC have achieved only limited success. A major bottleneck is the lack of robust protocols to define the key parameters and steps [109]. For example, there are no consensuses on methods for QD-antibody (QD-Ab) bioconjugation, tissue specimen preparation, multicolor QD staining, image processing and data quantification. So it is necessary to solve these problems, and let the QDs move further.
5. QDs Related Photodynamic Therapy for Cancer
Presently, the conventional types of cancer treatment (chemotherapy and radiation therapy), work by destroying fast-growing cells, but other types of fast-growing healthy cells (such as blood and hair cells) also can be damaged along with cancer cells, causing adverse reactions, or side effects. These side effects can range from fatigue and flu-like symptoms to hair loss and blood clotting problems. PDT developed in last century has become an FDA-approved therapy for different malignancies and with potential in other ailments such as coronary heart disease, AIDS and psoriasis [63].
Exploration of the use of light-activated drugs known as photosensitizers (PS) has been one of the most active areas of photomedical research in recent years [18–21,63,114,115]. PDT uses the combination of a photosensitizing drug and light in the presence of oxygen to cause selective damage to the targeting tissue. During PDT, reactive oxygen intermediates (ROI) is generated in the diseased cells by a simple and controllable light-activated process, which involves a photosensitizer that is capable of absorbing light appropriate wavelength and transfers energy or electron to oxygen or other molecules, and creates ROI such as singlet oxygen (1O2), hydroxyl radical (OH), super oxide anion (O2−) and hydrogen peroxide (H2O2). Then ROI will immediately react with vital biomolecules in cell organelles, leading to cell damage, mutation, death and photooxidation of cell constituents [19,20,63,114,115]. Singlet oxygen (1O2) is regarded as the main mediator of photo-induced cytotoxicity in PDT, which causes oxidation and degradation of cellular components, and ultimately cell apoptosis. [20,63,114,115] (Figure 4).
The standard PS drugs for PDT are porphyrin, phthalocyanines and chlorine derivatives. Porphyrin derivatives are the first generation photosensitizer. Despite the clinical success of porphyrin derivatives, some of their disadvantages like prolonged cutaneous photosensitivity, chemical impurity and weak absorption at therapeutic wavelengths have inspired the development of new PDT photosensitizers with improved optical and chemical properties. Phthalocyanines derivatives have favorable photophysical and chemical properties, which include strong absorbance at long wavelengths and chemical tunability through substituent addition on the periphery of the macrocycle or on the axial ligands. However, like most photosensitizing agents, these PS have poor solubility in water and tend to aggregate in aqueous solutions, which can result in loss of photochemical activity and affect their cell penetrating properties [63]. To resolve such issues nanoparticles are currently being explored as potential delivery systems for PDT photosensitizers or directly as PDT agents. The novel QDs-PS conjugates are used as a high ratio of PDT agents and anticancer targeting antibodies, where QDs can act as nanoscaffolds and solubilizers. They can also function as "energy-harvesting antenna" for PDT therapy due to their large one- or two-photon absorption cross-sections. Thus, QDs can be efficiently exited even deep within tissues and sensitized proximal PDT agents via energy transfer from QDs to PDT [21].
The novel QDs-PS conjugates showed many advantages over conventional PS drugs [17–21,63,114,115]: (1) they are species with well-defined size, shape, and composition, and can be synthesized by relatively simple and inexpensive methods; (2) they have been shown to be nontoxic in the absence of light but have the potential to be cytotoxic under irradiation; (3) they have photostability, and tunable and strong absorption, which can be tuned from the UV their composition and size; (4) the surface coating of QDs can be modified to enable them to become water soluble, biocompatible and target-specific.
However, researchers should be further investigated on the basis of predominances of the QDs-PS compared to the convention PS drugs. Despite many desirable properties of QDs for PDT, there still remain several important issues that need to be addressed to fully assess their applicability as PS in PDT. One major issue is the toxicity profile of the QDs inside the cells and their overall photostability once exposed to biological environments [63]. Another important matter that should be carefully investigated is how their surface composition affects the photosensitization process. Still, QDs-PS conjugates for cancer therapy are only suitable to superficial tumours is also need to be resolved [18].
6. Conclusions and Outlook
In the last decade, the unique photophysical properties and functions of QDs have been widely investigated, making them one of the most promising nanomaterials. Their outstanding performances such as high fluorescence yields, stability against photobleaching and the size-dependent luminescence features of QDs provide broad variety of applications for QDs in many fields. By acting as fluorescent, and photoelectrochemical as well as electrochemical probes, various QDs-based optical and electrochemical bioanalysis have already been successfully explored for sensing a wide range of molecules with high sensitivity and specificity. Furthermore, as a biomedical label, QDs can make a worthy contribution to the development of new diagnostic and delivery systems due to their unique optical properties. By combination of functional biomolecule-nanoparticle hybrid systems and the optical imaging and biophysics, QDs have been used as optical reporter units of biocatalytic transformations and can probe intracellular processes in vitro. QDs as a novel probe for in vivo analysis and clinic therapy such as PDT open an attractive new field with promising prospectives in biomedicine.
This review was financially supported by the National Basic Research Program of China (2010CB732400), the National Natural Science Foundation of China (21075055), the Program for Six Peak Talents of Jiangsu province (66) and the Leading Medical Talents Program from Department of Health of Jiangsu Province.
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- Diagaradjane, P.; Orenstein-Cardona, J.M.; Colón-Casasnovas, N.E.; Deorukhkar, A.; Shentu, S.; Kuno, N.; Schwartz, D.L.; Gelovani, J.G.; Krishnan, S. Imaging epidermal growth factor receptor expression in vivo: Pharmacokinetic and biodistribution characterization of a bioconjugated quantum dot nanoprobe. Clin. Cancer Res 2008, 14, 731–741, doi:10.1158/1078-0432.CCR-07-1958. 18245533
- Dudu, V.; Rotari, V.; Vazquez, M. Targeted extracellular nanoparticles enable intracellular detection of activated epidermal growth factor receptor in living brain cancer cells. Nanomedicine 2011, 7, 896–903, doi:10.1016/j.nano.2011.05.002. 21683807
- Chakraborty, S.K.; Fitzpatrick, J.A.; Phillippi, J.A.; Andreko, S.; Waggoner, A.S.; Bruchez, M.P.; Ballou, B. Cholera toxin B conjugated quantum dots for live cell labeling. Nano Lett 2007, 7, 2618–2626, doi:10.1021/nl0709930. 17663586
- Jaiswal, J.K.; Goldman, E.R.; Mattoussi, H.; Simon, S.M. Use of quantum dots for live cell imaging. Nat. Methods 2004, 1, 73–78, doi:10.1038/nmeth1004-73. 16138413
- Rajan, S.S.; Liu, H.Y.; Vu, T.Q. Ligand-bound quantum dot probes for studying the molecular scale dynamics of receptor endocytic trafficking in live cells. ACS Nano 2008, 2, 1153–1166, doi:10.1021/nn700399e. 19206333
- Rajan, S.S.; Vu, T.Q. Quantum dots monitor TrkA receptor dynamics in the interior of neural PC12 cells. Nano Lett 2006, 6, 2049–2059, doi:10.1021/nl0612650. 16968024
- Schroeder, J.E.; Shweky, I.; Shmeeda, H.; Banin, U.; Gabizon, A. Folate-mediated tumor cell uptake of quantum dots entrapped in lipid nanoparticles. J. Control. Release 2007, 124, 28–34, doi:10.1016/j.jconrel.2007.08.028. 17928088
- Dudu, V.; Ramcharan, M.; Gilchrist, M.L.; Holland, E.C.; Vazquez, M. Liposome delivery of quantum dots to the cytosol of live cells. J. Nanosci. Nanotechnol 2008, 8, 2293–2300, doi:10.1166/jnn.2008.185. 18572640
- Voura, E.B.; Jaiswal, J.K.; Mattoussi, H.; Simon, S.M. Tracking metastatic tumor cell extravasation with quantum dot nanocrystals and fluorescence emission-scanning microscopy. Nat. Med 2004, 10, 993–998, doi:10.1038/nm1096. 15334072
- Duan, H.; Nie, S. Cell-penetrating quantum dots based on multivalent and endosome-disrupting surface coatings. J. Am. Chem. Soc 2007, 129, 3333–3338, doi:10.1021/ja068158s. 17319667
- Fuente, J.M.; Fandel, M.; Berry, C.C.; Riehle, M.; Cronin, L.; Aitchison, G.; Curtis, A.S. Quantum dots protected with tiopronin: A new fluorescence system for cell-biology studies. ChemBioChem 2005, 6, 989–991, doi:10.1002/cbic.200500071. 15852337
- Farias, PM.; Santos, B.S.; Menezes, F.D. Core-shell CdS/Cd(OH)2 quantum dots: Synthesis and bioconjugation to target red cells antigens. J. Microsc 2005, 219, 103–108, doi:10.1111/j.1365-2818.2005.01501.x. 16176249
- Coulon, J.; Thouvenin, I.; Aldeek, F.; Balan, L.; Schneider, R. Glycosylated quantum dots for the selective labelling of Kluyveromyces bulgaricus and Saccharomyces cerevisiae yeast strains. J. Fluoresc 2010, 20, 591–597, doi:10.1007/s10895-009-0590-8. 20058182
- Bharali, D.J.; Lucey, D.W.; Jayakumar, H.; Pudavar, H.E.; Prasad, P.N. Folate-receptor-mediated delivery of InP quantum dots for bioimaging using confocal and two-photon microscopy. J. Am. Chem. Soc 2005, 127, 11364–11371, doi:10.1021/ja051455x. 16089466
- Clarke, S.; Nadeau, J.; Bahcheli, D.; Zhang, Z.; Hollmann, C. Quantum dots as phototoxic drugs and sensors of specific metabolic processes in living cells. Proceedings of the 27th Annual International Conference of the Engineering in Medicine and Biology Society, Shanghai, China, 17–18 January 2005. Volume 1; pp. 504–507.
- Xue, X.; Pan, J.; Xie, H.; Wang, J.; Zhang, S. Fluorescence detection of total count of Escherichia coli and Staphylococcus aureus on water-soluble CdSe quantum dots coupled with bacteria. Talanta 2009, 77, 1808–1813, doi:10.1016/j.talanta.2008.10.025. 19159803
- Clarke, S.J.; Hollmann, C.A.; Zhang, Z.J.; Suffern, D.; Bradforth, S.E.; Dimitrijevic, N.M.; Minarik, W.G.; Nadeau, J.L. Photophysics of dopamine-modified quantum dots and effects on biological systems. Nat. Mater 2006, 5, 409–417, doi:10.1038/nmat1631. 16617348
- Dubertret, B.; Skourides, P.; Norris, D.J.; Noireaux, V.; Brivanlou, A.H.; Libchaber, A. In vivo imaging of quantum dots encapsulated in phospholipid micelles. Science 2002, 298, 1759–1762, doi:10.1126/science.1077194. 12459582
- Medintz, I.L.; Pons, T.; Delehanty, J.B.; Susumu, K.; Brunel, F.M.; Dawson, P.E.; Mattoussi, H. Intracellular delivery of quantum dot-protein cargos mediated by cell penetrating peptides. Bioconjug. Chem 2008, 19, 1785–1795, doi:10.1021/bc800089r. 18681468
- Cai, W.B.; Shin, D.W.; Chen, K.; Gheysens, O.; Cao, Q.Z.; Wang, S.X. Peptide-labeled nearinfrared quantum dots for imaging tumor vasculature in living subjects. Nano Lett 2006, 6, 669–676, doi:10.1021/nl052405t. 16608262
- Yu, X.; Chen, L.; Li, K.; Li, Y.; Xiao, S.; Luo, X. Immunofluorescence detection with quantum dot bioconjugates for hepatoma in vivo. J. Biomed. Opt 2007, 12, 1–5.
- Weng, K.C.; Noble, C.O.; Papahadjopoulos-Sterberg, B.; Chen, F.F.; Drummond, D.C.; Kirpotin, D.B. Targeted tumor cell internalization and imaging of multifunctional quantum dot-conjugated immunoliposomes in vitro and in vivo. Nano Lett 2008, 8, 2851–2857, doi:10.1021/nl801488u. 18712930
- Janib, S.M.; Moses, A.S.; MacKay, J.A. Imaging and drug delivery using theranostic nanoparticles. Adv. Drug Deliv. Rev 2010, 62, 1052–1063, doi:10.1016/j.addr.2010.08.004. 20709124
- Matsuno, A.; Mizutani, A.; Okinaga, H.; Takano, K.; Yamada, S.; Yamada, S.M.; Nakaguchi, H.; Hoya, K.; Murakami, M.; Takeuchi, M.; Sugaya, M.; Itoh, J.; Takekoshi, S.; Osamura, R.Y. Molecular morphology of pituitary cells, from conventional immunohistochemistry to fluorescein imaging. Molecules 2011, 16, 3618–3635, doi:10.3390/molecules16053618. 21540793
- Byers, R.J.; Hitchman, E.R. Quantum dots brighten biological imaging. Prog. Histochem. Cytochem 2011, 45, 201–237, doi:10.1016/j.proghi.2010.11.001. 21196026
- Isse, K.; Grama, K.; Abbott, I.M.; Lesniak, A.; Lunz, J.G.; Lee, W.M.; Specht, S.; Corbitt, N.; Mizuguchi, Y.; Roysam, B.; Demetris, A.J. Adding value to liver (and allograft) biopsy evaluation using a combination of multiplex quantum dot immunostaining, high-resolution whole-slide digital imaging, and automated image analysis. Clin. Liver Dis 2010, 14, 669–685, doi:10.1016/j.cld.2010.07.004. 21055689
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- Yaghini, E.; Seifalian, A.M.; MacRobert, A.J. Quantum dots and their potential biomedical applications in photosensitization for photodynamic therapy. Nanomedicine 2009, 4, 353–363, doi:10.2217/nnm.09.9. 19331542
- Rakovich, A.; Savateeva, D.; Rakovich, T.; Donegan, J.F.; Rakovich, Y.P.; Kelly, V.; Lesnyak, V.; Eychmüller, A. CdTe quantum dot/dye hybrid system as photosensitizer for photodynamic therapy. Nanoscale Res. Lett 2010, 5, 753–760, doi:10.1007/s11671-010-9553-x. 20671788
|Table 1. Selected strategies for the intracellular delivery of QDs.
|Targeted Cells
|Passive uptake
|Electrostatic interactions
|Human macrophages
|Breast cancer (MDA-MB-231)
|Human melanoma cells (LU1205)
|Facilitated delivery
|Human embryonic kidney
|Mesenchymal stem cells
|Jurkat cells
|Pep-1 (Chariot)
|Vascular endothelial cells
|RGD motify
|Fibroblast (NIH 3T3)
|Epidermoid carcinoma
|Human pancreatic cancer
|Breast cancer (MCF-7)
|Mesenchymal stem cells
|Chinese hamster ovary
|Medulloblastoma tumors
|Glioma tumors
|Cholera toxin B
|PC12 neural cells
|Lipid polymers
|Mouse lymphoma
|A549 epithelial lung HeLa
|Small molecule
|S. cerevisiae (Baker's yeast)
|Epidermal carcinoma
|Bacteria (Bacillus subtilis, E. coli)
|A9 mouse fibroblast with transfected dopamine receptor
|Active Delivery
|Mouse neural stem progenitor cells
|Xenopus embryo
|Human embryonic kidney
© 2011 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license (http://creativecommons.org/licenses/by/3.0/).


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BENTON HARBOR Two top political leaders in Benton Harbor are facing fines for the late filing of three forms required under Michigan's Campaign Finance Act.
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Bowens' infraction came from the Citizens to Save Benton Harbor commitee , which was formed to support the city income tax proposal on the November 2013 ballot.


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Posts by gtaube
2 posts • joined 6 Jun 2011
Million-plus IOPS: Kaminario smashes IBM in DRAM decimation
Architecture Matters More than Media Type
One of our primary intentions in going through the SPC process was to test the SPEAR architecture's scale-out capabilities. The SPC-1 put the K2 through a heavy workload over a 24-hour period. It came through with flying colors showing that Kaminario allows you to achieve high-end performance without suffering from bottlenecks of any type.
Some comments have focused on the fact that the K2 configuration included DRAM. So of course, the IOPS were going to be super fast. From our vantage point, the media type matters less than the architecture. We happened to certify the K2-D in this test result, but SPEAR will also enable high-level, scalable storage performance for Flash. That is the beauty of having a powerful and flexible architecture. It provides you with more choices and the ability to adapt as newer memory types emerge -- All in an environment with advanced data protection.
Part flash, all flash or dedicated flash?
VP Kaminario
This is an excellent comparison of the pros and cons of different types of SSD deployment. One point I'd like to make sure the reader understands is that many of the limitations of SSD described here are simply irrelevant when it comes to DRAM. DRAM has none of the life limitations of SSD and has far superior write performance. DRAM performance does not degrade over time as Flash performance does and DRAM does not die after a specified number of writes. Like the Energizer bunny, DRAM just keeps working the same way it did on day one. Those are important things to consider when choosing between a flash and DRAM SSD solution. As you mention, it's also important to understand the superior performance characteristics of purpose built appliances, which are not constrained by the I/O limitations of disk-like architecture.
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What's NewThis version has:
'ûô 8 new dog heads
'ûô some dog heads have funny expressions
'ûô bug and crash fixes
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Cool and funny app ... Need more dog faces and please extend it to other animals like pigs , tiger ... Etc.
App Changes
May 28, 2011 New version 1.1.0
January 27, 2011 Initial Release


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Herbed macaroni parmesan
Updated On: Oct 02 2014 06:14:25 AM EDT
Makes 4 servings
This very simple dish is one of my favorite "emergency" dinners that I make when time is especially limited. Use short cuts or strands of other Italian pastas you might have on hand. When time permits, I expand on the simple recipe and add other vegetables, such as strips of grilled portobello mushrooms.
8 ounces elbow macaroni
3 tablespoons unsalted butter
½ cup freshly grated Parmesan cheese
1 plum tomato, cut into ½-inch cubes
2 tablespoons minced fresh basil or 2 teaspoons dried basil
2 tablespoons minced fresh flat-leaf parsley
Dash of salt, or to taste
Dash of freshly ground pepper, or to taste
Bring a large pot of water to a boil over high heat; add the macaroni. When the water returns to a boil, stir occasionally to separate the macaroni. Reduce the heat to medium-high and cook until al dente, about 6 to 8 minutes, or according to package instructions.
When the macaroni is done, drain well; return to the pot. Add the butter; stir until it melts. Add the remaining ingredients and toss. Taste and adjust the seasoning.
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Sylva Cabin Rental Photos and Description
2 bedrooms, 1 bath, sleeps 4-6
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Hike through the acres of woods that surround the cabin, or fish for rainbow and speckled trout in the bold creek just down the road. In the evenings, you can roast marshmallows at the fire pit where you can sometimes hear an old Barred Owl hooting in the trees nearby. Take a long stroll up the East Fork creek where 100+ year old farm houses, grazing horses and cattle, and rustic old barns and silos whisper the stories from a bye gone era.
Newly renovated, this romantic little A-Frame log cabin has all the modern comforts of home while maintaining the rustic nostalgia of a cozy little cabin in the woods! The cabin has a queen-sized bed in the downstairs bedroom and a second queen-sized bed in the loft bedroom. There is also a sleeper sofa in the living area that helps to accommodate up to 6 people. A fully equipped kitchen and separate laundry room have everything you will need for your stay. The cabin also has wireless internet access throughout and a flat screen HDTV with Directv programming. Outside, there is a Weber gas grill, dining and picnic tables and plenty of seating for enjoying meals outside. Also, our newly installed 6 person hot tub is perfect for a relaxing soak after a long day of fun in the mountains.
Conveniently located only 10 minutes from the charming town of historic Dillsboro and 15 minutes from Sylva, Franklin, and Western Carolina University. The towns of Cherokee and Waynesville are just a 30 minute or less drive away.
If your looking for a cozy place to relax, decompress, and get back to nature, you will find everything you're looking for in the Little Cove!
- Suitability:
- children welcome
- non smoking only
- pets considered
About Kimberly Gray
My husband and I live and work in Sylva and are busy parents to our 4 small children. My husband works for the phone company and I am a potter that enjoys playing in the mud all day. We feel very blessed to be able to live and raise our children in these beautiful mountains.
Kimberly Gray purchased this cabin in 2007
Why Kimberly Gray chose Sylva
This property has been in my family for over 200 years. Growing up in Maryland, I have many fond childhood memories of my family's regular visits to the mountains and staying in the Little Cove. Playing in the woods and catching crawdads in the creek with my brother were some of my favorite things to do.
Originally built in the 1970's, the aging Little Cove cabin was in need of some TLC. As a result, a few years ago, my husband and I began a 2 year 'rebuild'. The result was a brand new home with the nostalgic charm of an old mountain A-Frame cabin. We are proud of the hard-work and love we've poured into this cabin and hope that many families will now make special memories of their own in the Little Cove.
Guestbook comments from the owner
Very cozy and relaxing cabin. The perfect vacation spot in the mountains! Great job!


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There is some good news for those out of work.
A job fair, featuring dozens of companies, takes place on Tuesday.
Thirty-six companies will be featured.
Combined, the companies are looking to hire more than a 1,000 employees.
The Linking Michiana Job Fair runs from 2:30 to 5:30 p.m. at Howe Military Academy.
Applicants should bring several copies of their resumes.


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Head on over to dmacrye Tech to read my new guest post regarding the app organizer App 2 SD for Android: You've just bought the latest, greatest Android phone and proceeded to download every cool app out there. Then you…
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