Fetal and neonatal immune thrombocytopenia (FNIT) is a severe bleeding disorder caused by maternal antibody-mediated destruction of fetal/neonatal platelets. It is the most common cause of severe thrombocytopenia in neonates, but the frequency of FNIT-related miscarriage is unknown, and the mechanism(s) underlying fetal mortality have not been explored. Furthermore, although platelet αIIbβ3 integrin and GPIbα are the major antibody targets in immune thrombocytopenia, the reported incidence of anti-GPIbα-mediated FNIT is rare. Here, we developed mouse models of FNIT mediated by antibodies specific for GPIbα and β3 integrin and compared their pathogenesis. We found, unexpectedly, that miscarriage occurred in the majority of pregnancies in our model of anti-GPIbα-mediated FNIT, which was far more frequent than in anti-β3-mediated FNIT. Dams with anti-GPIbα antibodies exhibited extensive fibrin deposition and apoptosis/necrosis in their placentas, which severely impaired placental function. Furthermore, anti-GPIbα (but not anti-β3) antiserum activated platelets and enhanced fibrin formation in vitro and thrombus formation in vivo. Importantly, treatment with either intravenous IgG or a monoclonal antibody specific for the neonatal Fc receptor efficiently prevented anti-GPIbα-mediated FNIT. Thus, the maternal immune response to fetal GPIbα causes what we believe to be a previously unidentified, nonclassical FNIT (i.e., spontaneous miscarriage but not neonatal bleeding) in mice. These results suggest that a similar pathology may have masked the severity and frequency of human anti-GPIbα-mediated FNIT, but also point to possible therapeutic interventions.

Delphinidin-3-glucoside (Dp-3-g) is one of the predominant bioactive compounds of anthocyanins in many plant foods. Although several anthocyanin compounds have been reported to be protective against cardiovascular diseases (CVDs), the direct effect of anthocyanins on platelets, the key players in atherothrombosis, has not been studied. The roles of Dp-3-g in platelet function are completely unknown. The present study investigated the effects of Dp-3-g on platelet activation and several thrombosis models in vitro and in vivo. We found that Dp-3-g significantly inhibited human and murine platelet aggregation in both platelet-rich plasma and purified platelets. It also markedly reduced thrombus growth in human and murine blood in perfusion chambers at both low and high shear rates. Using intravital microscopy, we observed that Dp-3-g decreased platelet deposition, destabilized thrombi, and prolonged the time required for vessel occlusion. Dp-3-g also significantly inhibited thrombus growth in a carotid artery thrombosis model. To elucidate the mechanisms, we examined platelet activation markers via flow cytometry and found that Dp-3-g significantly inhibited the expression of P-selectin, CD63, CD40L, which reflect platelet α- and δ-granule release, and cytosol protein secretion, respectively. We further demonstrated that Dp-3-g downregulated the expression of active integrin αIIbβ3 on platelets, and attenuated fibrinogen binding to platelets following agonist treatment, without interfering with the direct interaction between fibrinogen and integrin αIIbβ3. We found that Dp-3-g reduced phosphorylation of adenosine monophosphate-activated protein kinase, which may contribute to the observed inhibitory effects on platelet activation. Thus, Dp-3-g significantly inhibits platelet activation and attenuates thrombus growth at both arterial and venous shear stresses, which likely contributes to its protective roles against thrombosis and CVDs.

Platelet αIIbβ3 integrin and its ligands are essential for thrombosis and hemostasis, and play key roles in myocardial infarction and stroke. Here we show that apolipoprotein A-IV (apoA-IV) can be isolated from human blood plasma using platelet β3 integrin-coated beads. Binding of apoA-IV to platelets requires activation of αIIbβ3 integrin, and the direct apoA-IV-αIIbβ3 interaction can be detected using a single-molecule Biomembrane Force Probe. We identify that aspartic acids 5 and 13 at the N-terminus of apoA-IV are required for binding to αIIbβ3 integrin, which is additionally modulated by apoA-IV C-terminus via intra-molecular interactions. ApoA-IV inhibits platelet aggregation and postprandial platelet hyperactivity. Human apoA-IV plasma levels show a circadian rhythm that negatively correlates with platelet aggregation and cardiovascular events. Thus, we identify apoA-IV as a novel ligand of αIIbβ3 integrin and an endogenous inhibitor of thrombosis, establishing a link between lipoprotein metabolism and cardiovascular diseases.

Platelets are small anucleate cells generated from megakaryocytes in the bone marrow. After being released into the circulation, platelets play key roles in the surveillance of vascular injury, and can quickly adhere and aggregate at the site of injury, which are critical events for vascular repair and hemostasis. However, the same biological processes of platelet adhesion and aggregation may also cause thrombotic disorders. The formation of a platelet plug at sites of atherosclerotic lesion rupture is the most common mechanism leading to myocardial or cerebral infarction. Platelet-related deep vein thrombosis is also one of the leading causes of mortality worldwide. The contribution of several platelet receptors and their ligands has been highlighted in these processes. In platelet adhesion, particularly at high shear stress, GPIbα-von Willebrand factor (VWF) interaction may initiate this event, which is followed by GPVI signalling and firm platelet adhesion mediated by members of the integrin family, such as β3 (αIIbβ3) and β1 (α2β1, α5β1) integrins. In platelet aggregation, although GPIbα-VWF, P selectin-sulfatides, and other molecules, may be involved, the process is mainly mediated by β3 (αIIbβ3) integrin and its ligands, such as fibrinogen and VWF. It is intriguing that platelet adhesion and aggregation still occur in mice lacking both fibrinogen and VWF, suggesting that other unforeseen molecule(s) may also be important in these processes. Identification and characterization of these molecules will enrich our knowledge in the basic science of hemostasis and thrombosis, and may lead to the development of new therapies against bleeding disorders and thrombotic diseases.

In this paper, a fractional-order memristive chaotic circuit system is defined according to memristor circuit. The dynamic characteristics are analyzed through the phase diagram, bifurcation diagram, and Lyapunov exponent spectrum, and the randomness of the chaotic pseudo-random sequence is tested by NIST SP800-22. Based on this fractional-order memristive chaotic circuit, we propose a novel color image compression-encryption algorithm. In this algorithm, compression sensing (CS) algorithm is used for compression image, and then using Zigzag confusion, add modulus and BitCircShift diffuse encrypt the image. The theoretical analysis and simulation results indicate that the proposed compression and encryption scheme has good compression performance, reconstruction effect, and higher safety performance. Moreover, it also shows that the new algorithm facilitates encryption, storage, and transmission of image information in practical applications. INDEX TERMSColor image encryption, compression sensing (CS), zigzag confusion, add modulus and BitCircShift diffuse, fractional-order memristive chaotic circuit.

LTE-Advanced system which based on orthogonal frequency division multiplexing (OFDM) can eliminate intra-cell interference but still can not mitigate inter-cell interference (ICI). Coordinated Multi-Point transmission/reception (CoMP) is one of the candidate techniques for LTE-Advanced systems to increase the cell average and cell edge user throughput in the both uplink and downlink. Although CoMP naturally increases system complexity, it has potentially significant capacity and coverage benefits, making it worth a more detailed consideration. In this paper, we present our initial views on the application of BBU+RRU based CoMP system to LTE-Advanced. Furthermore, simulation results for uplink show that the CoMP joint processing can bring significant gains to both the average sector throughput and the 5% of user throughput.

(http://translationalmedicine.stanford.edu/Mass-Conductor/FDR.html).

Preterm labor (PTL) is frequently associated with inflammation. We hypothesized that biomarkers during pregnancy can identify pregnancies most at risk for development of PTL. An inflammation-induced mouse model of PTL was used. Surfaceenhanced laser desorption/ionization time-of-flight mass spectrometry was used to analyze and compare the plasma protein (PP) profile between CD-1 mice injected intrauterine with either lipopolysaccharide (LPS) or PBS on d 14.5 of gestation. The median differences of normalized PP peaks between the two groups were determined using the Mann-Whitney U test and the false discovery rate. In a second series of experiments, both groups of mice were injected with a lower dose of LPS. A total of 1665 peaks were detected. Thirty peaks were highly differentially expressed (p Ͻ 0.0001) between the groups. Two 11 kDa protein peaks were identified by MALDI-TOF/TOF-MS and confirmed to be mouse serum amyloid A (SAA) 1 and 2. Plasma SAA2 levels were increased in LPS-treated animals compared with controls and in LPS-treated animals that delivered preterm vs. those that delivered at term. SAA2 has the potential to be a plasma biomarker that can identify pregnancies at risk for development of PTL. (Pediatr Res 66: 11-16, 2009) P reterm birth is the most important cause of neonatal morbidity and mortality in the United States (1-3). Despite several interventions including use of various tocolytics, antibiotics, and monitoring uterine contractions the incidence of preterm birth in the United States has not decreased in the past few decades and is currently at 12.7% (4,5) (Births. Preliminary data for 2005 http://www.cdc.gov/nchs/). More recently, the use of progesterone has been shown to be effective in prevention of preterm labor (PTL) in a select group of women. However, the mechanism by which this occurs is still unknown (6,7). One of the problems in preventing PTL is our inability to accurately identify which pregnancies are most likely to be complicated by PTL (8). Detection of a biomarker during pregnancy may assist in identifying an at risk population of pregnant women in whom a particular treatment can be studied. It can also help us gain important insights into the molecular pathways resulting in PTL.There is strong evidence to suggest that intrauterine (IU) infection or inflammation has a strong association with preterm delivery (3,9 -11). It is estimated that an overt or subclinical IU inflammation is present in close to 25-75% of births that result from spontaneous PTL (12,13). The timing of onset of IU inflammation and whether these markers of inflammation are present in the plasma is unknown. A sensitive diagnostic marker identified in early pregnancy may assist in early application of preventive therapies for women at risk for developing PTL.Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF/MS) is a high throughput proteomics technology that has been used for discovery of potential biomarkers of diseases (14 -22).In this study, we used a m...