An Improved Performance Radar Sensor for K-Band Automotive Radars.

This paper presents a new radar sensor configuration of a planar grid antenna array (PGAA) for automotive ultra-wideband (UWB) radar applications. For system realisation, the MIMO concept is adopted. The proposed antenna is designed to operate over the 24 GHz frequency band. It is based on split-ring resonator (SRR) elements to enhance the operating bandwidth and increase the antenna gain, leading to a better-performing radar system. The PGAA consists of thirty-one radiating elements, in which each element excitation is obtained using a common transmission line centre fed by a 50 Ω coaxial probe. By introducing a superstrate dielectric layer at a distance of λ/2 from the top of the antenna array, the PGAA gain and impedance bandwidth are further improved. The gain is improved by 2.7 dB to reach 16.5 dBi at 24 GHz, and the impedance bandwidth is enhanced to 9.3 GHz (37.7%). The measured impedance bandwidth of the proposed antenna array ranges from 20 GHz to 29.3 GHz for a reflection coefficient (S11) of less than -10 dB. The proposed antenna is validated for automotive applications.

CD86-based analysis enables observation of bona fide hematopoietic responses.

Hematopoiesis is a system that provides red blood cells (RBCs), leukocytes, and platelets, which are essential for oxygen transport, biodefense, and hemostasis; its balance thus affects the outcome of various disorders. Here, we report that stem cell antigen-1 (Sca-1), a cell surface marker commonly used for the identification of multipotent hematopoietic progenitors (Lin-Sca-1+c-Kit+ cells; LSKs), is not suitable for the analysis of hematopoietic responses under biological stresses with interferon production. Lin-Sca-1-c-Kit+ cells (LKs), downstream progenitors of LSKs, acquire Sca-1 expression upon inflammation, which makes it impossible to distinguish between LSKs and LKs. As an alternative and stable marker even under such stresses, we identified CD86 by screening 180 surface markers. The analysis of infection/inflammation-triggered hematopoiesis on the basis of CD86 expression newly revealed urgent erythropoiesis producing stress-resistant RBCs and intact reconstitution capacity of LSKs, which could not be detected by conventional Sca-1-based analysis.

Tissue injury and related mediators of pain exacerbation.

Tissue injury and inflammation result in release of various mediators that promote ongoing pain or pain hypersensitivity against mechanical, thermal and chemical stimuli. Pro-nociceptive mediators activate primary afferent neurons directly or indirectly to enhance nociceptive signal transmission to the central nervous system. Excitation of primary afferents by peripherally originating mediators, so-called "peripheral sensitization", is a hallmark of tissue injury-related pain. Many kinds of pro-nociceptive mediators, including ATP, glutamate, kinins, cytokines and tropic factors, synthesized at the damaged tissue, contribute to the development of peripheral sensitization. In the present review we will discuss the molecular mechanisms of peripheral sensitization following tissue injury.

Myeloid-like B cells boost emergency myelopoiesis through IL-10 production during infection.

Emergency myelopoiesis (EM) is a hematopoietic response against systemic infections that quickly supplies innate immune cells. As lymphopoiesis is strongly suppressed during EM, the role of lymphocytes in that process has not received much attention. Here, we found that myeloid-like B cells (M-B cells), which express myeloid markers, emerge in the bone marrow (BM) after the induction of EM. M-B cells were mainly derived from pre-B cells and preferentially expressed IL-10, which directly stimulates hematopoietic progenitors to enhance their survival and myeloid-biased differentiation. Indeed, lacking IL-10 in B cells, blocking IL-10 in the BM with a neutralizing antibody, and deleting the IL-10 receptor in hematopoietic progenitors significantly suppressed EM, which failed to clear microbes in a cecal ligation and puncture model. Thus, a distinct B cell subset generated during infection plays a pivotal role in boosting EM, which suggests the on-demand reinforcement of EM by adaptive immune cells.

An Antibody-Drug Conjugate That Selectively Targets Human Monocyte Progenitors for Anti-Cancer Therapy.

As hematopoietic progenitors supply a large number of blood cells, therapeutic strategies targeting hematopoietic progenitors are potentially beneficial to eliminate unwanted blood cells, such as leukemic cells and immune cells causing diseases. However, due to their pluripotency, targeting those cells may impair the production of multiple cell lineages, leading to serious side effects such as anemia and increased susceptibility to infection. To minimize those side effects, it is important to identify monopotent progenitors that give rise to a particular cell lineage. Monocytes and monocyte-derived macrophages play important roles in the development of inflammatory diseases and tumors. Recently, we identified human monocyte-restricted progenitors, namely, common monocyte progenitors and pre-monocytes, both of which express high levels of CD64, a well-known monocyte marker. Here, we introduce a dimeric pyrrolobenzodiazepine (dPBD)-conjugated anti-CD64 antibody (anti-CD64-dPBD) that selectively induces the apoptosis of proliferating human monocyte-restricted progenitors but not non-proliferating mature monocytes. Treatment with anti-CD64-dPBD did not affect other types of hematopoietic cells including hematopoietic stem and progenitor cells, neutrophils, lymphocytes and platelets, suggesting that its off-target effects are negligible. In line with these findings, treatment with anti-CD64-dPBD directly killed proliferating monocytic leukemia cells and prevented monocytic leukemia cell generation from bone marrow progenitors of chronic myelomonocytic leukemia patients in a patient-derived xenograft model. Furthermore, by depleting the source of monocytes, treatment with anti-CD64-dPBD ultimately eliminated tumor-associated macrophages and significantly reduced tumor size in humanized mice bearing solid tumors. Given the selective action of anti-CD64-dPBD on proliferating monocyte progenitors and monocytic leukemia cells, it should be a promising tool to target cancers and other monocyte-related inflammatory disorders with minimal side effects on other cell lineages.

Five-day pain management regimen using patient-controlled analgesia facilitates early ambulation after cardiac surgery.

PURPOSE: Excessive pain may interrupt early rehabilitation after cardiac surgery. The purpose of this study was to evaluate the efficacy of a longer patient-controlled analgesia (PCA) regimen for early ambulation after cardiac surgery. METHODS: This study was designed to be a retrospective, single-institutional (focusing on an urban, university-affiliated hospital), pre-post intervention survey. Fifty-nine patients undergoing elective cardiac surgery were included. A long pain management regimen (subcutaneous fentanyl PCA for up to 120 h) protocol was implemented for the postoperative care for adult cardiac surgery patients. Before implementing this extended protocol, the same PCA regimen was used for up to 40 h. Perioperative and postoperative management was similar for all patients. The number of days required to walk more than 100 m without assistance was recorded. Additional usage of analgesic drugs and pain intensity on movement were documented up to POD 5. RESULTS: Time required to walk more than 100 m without assistance was significantly shorter in the 120 h PCA group. Need for another analgesic regimen and pain score during the ambulation phase were significantly lower in the 120 h PCA than in the 40 h PCA group. Frequency of side effects was similar for both groups. CONCLUSION: Pain management using a PCA system can be recommended for patients during the ambulation period after cardiac surgery. Subcutaneous PCA with fentanyl is a safe and effective analgesic regimen for this purpose.

Peripheral sensitization caused by insulin-like growth factor 1 contributes to pain hypersensitivity after tissue injury.

Sensitization of primary afferent neurons is one of the most important components of pain hypersensitivity after tissue injury. Insulin-like growth factor 1 (IGF-1), involved in wound repair in injured tissue, also plays an important role in maintaining neuronal function. In the present study, we investigated the effect of tissue IGF-1 on nociceptive sensitivity of primary afferent neurons. Local administration of IGF-1 induced thermal and mechanical pain hypersensitivity in a dose-dependent manner, and was attenuated by IGF-1 receptor (IGF1R) inhibition. Tissue but not plasma IGF-1 levels, as determined by enzyme-linked immunosorbent assay, significantly increased after plantar incision. Immunohistochemistry revealed that IGF1R was predominantly expressed in neurons as well as in satellite glial cells in the dorsal root ganglion (DRG). Double-labeling immunohistochemistry showed that IGF1R expression colocalized with peripherin and TRPV1, but not with NF200 in DRG neurons. The IGF1R inhibitor successfully alleviated mechanical allodynia, heat hyperalgesia, and spontaneous pain behavior observed after plantar incision. Expression of phosphorylated Akt in DRG neurons significantly increased after plantar incision and was suppressed by IGF1R inhibition. These results demonstrate that increased tissue IGF-1 production sensitizes primary afferent neurons via the IGF1R/Akt pathway to facilitate pain hypersensitivity after tissue damage.