BACKGROUND & AIMS: :Uncontrolled fine generation during the milling process is a challenge for dry granulation by roller compaction. Here, we report the observation that ribbon thickness can significantly influence percentage of fines. Thus, among other parameters, ribbon thickness needs to be controlled for the development of a robust roller compaction process and ensure successful scale up.

背景与目标： : 碾磨过程中不受控制的精细产生是通过辊压进行干法造粒的挑战。在这里，我们报告了色带厚度会显着影响细粉百分比的观察结果。因此，除其他参数外，还需要控制色带厚度，以开发坚固的压辊压实工艺并确保成功扩大规模。

BACKGROUND & AIMS: INTRODUCTION:Mismatch negativity (MMN) is thought to reflect preattentive, automatic auditory processing. Reduced MMN amplitude is among the most robust findings in schizophrenia research. MMN generators have been shown to be located in the temporal and frontal cortices, which are key areas in the pathophysiology of schizophrenia. This study investigated whether frontotemporal cortical thickness was associated with reduced MMN current source density (CSD) strength in patients with schizophrenia. METHODS:Sixteen schizophrenia patients and 18 healthy controls (HCs) were examined using magnetoencephalography while they performed a passive auditory oddball paradigm. All participants underwent a T1 structural magnetic resonance imaging scan in a separate session. We evaluated MMN CSD and cortical thickness, and their associations, in the superior and transverse temporal gyri, as well as in the inferior and middle frontal gyri. RESULTS:Patients exhibited significantly reduced CSD strength in all temporal and frontal areas of interest relative to HCs. There was a positive correlation between CSD strength and cortical thickness in both temporal and frontal areas in HCs. However, schizophrenia patients showed negative correlations between CSD strength and cortical thickness in the bilateral inferior frontal gyri. Additionally, we found positive correlations between frontal cortical thickness and negative and total scores on the Positive and Negative Syndrome Scale (PANSS). CONCLUSIONS:Our findings provide evidence for deficient temporal and frontal MMN generators and a disruption of normal structure-function relationship in patients with schizophrenia.

背景与目标：

BACKGROUND & AIMS: :Menopausal hormone treatment (MHT) may limit progression of cardiovascular disease (CVD) but poses a thrombosis risk. To test targeted candidate gene variation for association with subclinical CVD defined by carotid artery intima-media thickness (CIMT) and coronary artery calcification (CAC), 610 women participating in the Kronos Early Estrogen Prevention Study (KEEPS), a clinical trial of MHT to prevent progression of CVD, were genotyped for 13,229 single nucleotide polymorphisms (SNPs) within 764 genes from anticoagulant, procoagulant, fibrinolytic, or innate immunity pathways. According to linear regression, proportion of European ancestry correlated negatively, but age at enrollment and pulse pressure correlated positively with CIMT. Adjusting for these variables, two SNPs, one on chromosome 2 for MAP4K4 gene (rs2236935, β = 0.037, P value = 2.36 × 10(-06)) and one on chromosome 5 for IL5 gene (rs739318, β = 0.051, P value = 5.02 × 10(-05)), associated positively with CIMT; two SNPs on chromosome 17 for CCL5 (rs4796119, β = -0.043, P value = 3.59 × 10(-05); rs2291299, β = -0.032, P value = 5.59 × 10(-05)) correlated negatively with CIMT; only rs2236935 remained significant after correcting for multiple testing. Using logistic regression, when we adjusted for waist circumference, two SNPs (rs11465886, IRAK2, chromosome 3, OR = 3.91, P value = 1.10 × 10(-04); and rs17751769, SERPINA1, chromosome 14, OR = 1.96, P value = 2.42 × 10(-04)) associated positively with a CAC score of >0 Agatston unit; one SNP (rs630014, ABO, OR = 0.51, P value = 2.51 × 10(-04)) associated negatively; none remained significant after correcting for multiple testing. Whether these SNPs associate with CIMT and CAC in women randomized to MHT remains to be determined.

背景与目标： : 更年期激素治疗 (MHT) 可能会限制心血管疾病 (CVD) 的进展，但会带来血栓形成的风险。为了测试与颈动脉内膜中层厚度 (CIMT) 和冠状动脉钙化 (CAC) 定义的亚临床CVD相关的靶向候选基因变异，610参加Kronos早期雌激素预防研究 (KEEPS) 的妇女，MHT预防CVD进展的临床试验，在抗凝剂，促凝剂，纤溶或先天免疫途径的764基因内对13,229单核苷酸多态性 (snp) 进行基因分型。根据线性回归，欧洲血统的比例呈负相关，但入学年龄和脉压与CIMT呈正相关。调整这些变量，两个snp，一个在2号染色体上的MAP4K4基因 (rs2236935，β = 0.037，p值 = 2.36 × 10(-06))，一个在5号染色体上的IL5基因 (rs739318，β = 0.051，p值 = 5.02 × 10(-05))，与CIMT呈正相关; CCL5 17号染色体上的两个snp (rs4796119，β = -0.043，p值 = 3.59 × 10(-05); rs2291299，β = -0.032，p值 = 5.59 × 10(-05)) 与CIMT呈负相关; 校正多重测试后，只有rs2236935仍然显著。使用逻辑回归，当我们调整腰围时，两个snp (rs11465886，IRAK2，3号染色体，OR = 3.91，p值 = 1.10 × 10(-04); 和rs17751769，SERPINA1，14号染色体，OR = 1.96，p值 = 2.42 × 10(-04)) 与> 0 Agatston单位的CAC评分呈正相关; 1个SNP (rs630014，ABO，OR = 0.51，p值 = 2.51 × 10(-04)) 呈负相关; 校正多重测试后无显著。这些snp是否与CIMT和CAC相关，在随机分配到MHT的女性中仍有待确定。

BACKGROUND & AIMS: Na(+)-Ca2+ exchanger-associated membrane currents were studied in cultured murine neocortical neurons, using whole-cell recording combined with intracellular perfusion. A net inward current specifically associated with forward (Na+(o)-Ca2+(i)) exchange was evoked at -40 mV by switching external 140 mM Li+ to 140 mM Na+. The voltage dependence of this current was consistent with that predicted for 3Na+1Ca2+ exchange. As expected, the current depended on internal Ca2+, and could be blocked by intracellular application of the exchanger inhibitory peptide, XIP. Raising internal Na+ from 3 to 20 mM or switching the external solution from 140 mM Li+ to 30 mM Na+ activated outward currents, consistent with reverse (Na+(i)-Ca2+(o)) exchange. An external Ca2(+)-sensitive current was also identified as associated with reverse Na(+)-Ca2+ exchange based on its internal Na+ dependence and sensitivity to XIP. Combined application of external Na+ and Ca2+ in the absence of internal Na+ triggered a 3.3-fold larger inward current than the current activated in the presence of 3 mM internal Na+, raising the intriguing possibility that Na(+)-Ca2+ exchangers might concurrently operate in both the forward and the reverse direction, perhaps in different subcellular locations. With this idea in mind, we examined the effect of excitotoxic glutamate receptor activation on exchanger operation. After 3-5 min of exposure to 100-200 microM glutamate, the forward exchanger current was significantly increased even when external Na+ was reduced to 100 mM, and the external Ca2(+)-activated reverse exchanger current was eliminated.

背景与目标： 使用全细胞记录结合细胞内灌注，在培养的鼠新皮层神经元中研究了Na ()-Ca2交换剂相关的膜电流。通过将外部140 mM Li切换到140 mM Na，在40 mV时诱发了与正向 (Na (o)-Ca2 (i)) 交换特别相关的净向内电流。该电流的电压依赖性与3Na 1Ca2交换的预测一致。如预期的那样，电流取决于内部Ca2，并且可以通过在细胞内应用交换抑制肽XIP来阻断电流。将内部Na + 从3升高到20 mm或将外部溶液从140 mM Li + 切换到30mm Na + 激活的外向电流，与反向 (Na +(i)-Ca2 +(o)) 交换一致。根据其内部Na依赖性和对XIP的敏感性，还确定了对外部Ca2 () 敏感的电流与反向Na ()-Ca2交换有关。在不存在内部Na的情况下组合施加外部Na和Ca2触发的内向电流比在3毫米内部Na存在下激活的电流大3.3倍，提出了Na ()-Ca2交换剂可能同时在正向和反向同时运行的有趣可能性，也许在不同的亚细胞位置。考虑到这一想法，我们研究了兴奋性谷氨酸受体激活对交换器操作的影响。暴露于100-200 microM谷氨酸3-5分钟后，即使外部Na降低到100 mM，正向交换电流也显着增加，并且消除了外部Ca2 () 激活的反向交换电流。

BACKGROUND & AIMS: :In Saccharomyces cerevisiae, diploid yeast cells follow a bipolar budding program, which depends on the two transmembrane glycoproteins Bud8p and Bud9p that potentially act as cortical tags to mark the cell poles. Here, we have performed systematic structure-function analyses of Bud8p and Bud9p to identify functional domains. We find that polar transport of Bud8p and Bud9p does not depend on N-terminal sequences but instead on sequences in the median part of the proteins and on the C-terminal parts that contain the transmembrane domains. We show that the guanosine diphosphate (GDP)/guanosine triphosphate (GTP) exchange factor Bud5p, which is essential for bud site selection and physically interacts with Bud8p, also interacts with Bud9p. Regions of Bud8p and Bud9p predicted to reside in the extracellular space are likely to confer interaction with the N-terminal region of Bud5p, implicating indirect interactions between the cortical tags and the GDP/GTP exchange factor. Finally, we have identified regions of Bud8p and Bud9p that are required for interaction with the cortical tag protein Rax1p. In summary, our study suggests that Bud8p and Bud9p carry distinct domains for delivery of the proteins to the cell poles, for interaction with the general budding machinery and for association with other cortical tag proteins.

背景与目标： : 在酿酒酵母中，二倍体酵母细胞遵循双极出芽程序，该程序取决于两种跨膜糖蛋白Bud8p和Bud9p，它们可能充当皮质标签来标记细胞极。在这里，我们对Bud8p和Bud9p进行了系统的结构功能分析，以识别功能域。我们发现Bud8p和Bud9p的极性转运不依赖于N端序列，而是依赖于蛋白质中值部分和包含跨膜结构域的C端部分的序列。我们表明，鸟苷二磷酸 (GDP)/鸟苷三磷酸 (GTP) 交换因子Bud5p对于芽位点选择至关重要，并且与Bud8p物理相互作用，也与Bud9p相互作用。预测驻留在细胞外空间中的Bud8p和Bud9p区域可能会与Bud5p的N端区域产生相互作用，从而暗示皮质标签与GDP/GTP交换因子之间的间接相互作用。最后，我们确定了与皮质标签蛋白Rax1p相互作用所需的Bud8p和Bud9p区域。总而言之，我们的研究表明Bud8p和Bud9p具有不同的结构域，用于将蛋白质传递到细胞极，与一般的出芽机制相互作用以及与其他皮质标签蛋白结合。

BACKGROUND & AIMS: OBJECTIVE:To investigate cortical representation of articulation of the bilabial plosive in patients with cleft lip and palate. DESIGN:We examined cortical representation for /pa/-articulation in cleft lip and palate patients using blood oxygenation level-dependent functional magnetic resonance imaging. SUBJECTS:Data from four postsurgical adult cleft lip and palate patients were compared with those from six healthy volunteers. RESULTS:Activation foci were found in the bilateral primary sensorimotor cortex in all cleft lip and palate patients, as in the controls. The sensorimotor cortex ipsilateral to the side of cleft lip and palate showed greater activation in unilateral cleft lip and palate patients, whereas the sensorimotor cortex contralateral to the side on which cheiloplasty had been performed earlier showed greater activation in a bilateral cleft lip and palate patient. CONCLUSIONS:The results suggest that there may be an ipsilateral dominance in cortical representation during bilabial articulation to the side of the cleft in the upper lip.

背景与目标：

BACKGROUND & AIMS: :Cortical cavity lesions and lateral ventricular injections of quinolinic acid, a NMDA receptor agonist, induce Fos and Fos-related antigens (FRAs) throughout ipsilateral adult rat brain cortex in similar patterns. c-fos mRNA, assessed using in situ hybridization, was induced by 1 h and disappeared between 3 and 8 h following cortical lesions. Fos proteins, detected using a specific monoclonal antibody, were induced by 1 h and disappeared by 4 h after cortical lesions. FRA proteins, detected using polyclonal antibodies, were induced between 1 and 4 h and persisted for at least 72 h following focal cortical injury. Intraventricular injections of CPP, a competitive NMDA receptor antagonist, completely blocked the induction of these nuclear proteins in cortex ipsilateral to the focal cortical lesions--except around the injury site itself. Intraventricular injections of quisqualate, a non-NMDA glutamate analogue, induced Fos in hippocampus but not in cortex. These data show that NMDA receptors mediate the induction of Fos and FRAs following cortical injury. It is proposed that local cortical injury releases excitatory amino acids that act at NMDA receptors to initiate spreading depression and that the resultant depolarization induces Fos in neurons throughout the cortex. Since Fos and FRAs are proteins that regulate the expression of target genes, they could mediate long-term biochemical adaptations in neurons following cortical injury.

背景与目标： : 皮质腔病变和侧脑室注射喹啉酸 (一种NMDA受体激动剂) 以相似的方式在同侧成年大鼠大脑皮层中诱导Fos和Fos相关抗原 (fra)。使用原位杂交评估的c-fos mRNA在1小时内被诱导，并在皮质病变后3至8小时内消失。使用特异性单克隆抗体检测到的Fos蛋白在1小时内被诱导，并在皮质病变后4小时消失。使用多克隆抗体检测到的FRA蛋白在1至4小时之间被诱导，并在局灶性皮质损伤后持续至少72小时。脑室内注射CPP (一种竞争性NMDA受体拮抗剂) 完全阻断了局灶性皮质病变同侧皮质中这些核蛋白的诱导-除了损伤部位本身周围。脑室内注射非NMDA谷氨酸类似物quisqualate会在海马中诱导Fos，但在皮质中不诱导Fos。这些数据表明，NMDA受体介导皮质损伤后Fos和fra的诱导。有人提出，局部皮层损伤会释放起NMDA受体作用的兴奋性氨基酸，从而引发扩散抑制，并且由此产生的去极化会在整个皮层的神经元中诱导Fos。由于Fos和fra是调节靶基因表达的蛋白质，因此它们可以介导皮层损伤后神经元的长期生化适应。

BACKGROUND & AIMS: INTRODUCTION:New diagnostic tools such as the retinal thickness analyzer (RTA), optical coherence tomography (OCT), and topographic angiography (TAG) were introduced into clinical ophthalmology during the last years giving the examiner new insights into anatomical and functional aspects of macular disease. In this study, advantages and disadvantages of the new imaging methods have been evaluated in patients with serous (sPED) and fibrovascular pigment epithelial detachments (fPED) secondary to age-related macular degeneration (AMD). METHODS:TAG, using fluorescein angiography (FA), provides a three-dimensional profile of the fluorescein pattern based on the analysis of a set of 32 confocal images over a depth of 4 mm. RTA and OCT provide cross-sectional images of the neurosensory retina and the retinal pigment epithelium-choriocapillary complex as well as retinal thickness data encoded in a false color map. We compared and evaluated these modalities in 15 patients with fPED and 15 patients with sPED secondary to AMD. RESULTS:In patients with classic fPED, TAG detected neovascular structures and delineated their configuration. In sPEDs, pooling of extravascular fluid was detected in a dome-shaped configuration. OCT provided detailed information on the neurosensory retina's structures but failed to detect the neovascular membrane in fPED. Mapping the retinal thickness, RTA and OCT both failed to detect the PED and showed typical algorithm error-based patterns. CONCLUSION:TAG OCT and RTA are useful imaging modalities in the evaluation of AMD cases. TAG visualizes the vascular configuration, dynamic perfusion, and leakage changes. OCT and RTA are able to complementarily document intra-, subretinal, and sub-RPE fluid accumulation secondary to CNV. However, OCT seems to be more efficient in imaging AMD-related pathologies than RTA, as this modality is often compromised by intra- or subretinal structural abnormalities. Nevertheless, all modalities may provide further valuable insight into AMD pathogenesis, enhance diagnostic quality, and improve the assessment of therapeutic effects.

背景与目标：

BACKGROUND & AIMS: :The hierarchical development of the primate visual cortex and associated streams remains somewhat of a mystery. While anatomical, physiological, and psychological studies have demonstrated the early maturation of the dorsal "where"/"how" or motion cortical stream, little is known about the circuitry responsible. The influence of the retinogeniculostriate pathway has been investigated, but little attention has been paid to the role of two more recently described disynaptic retinothalamic projections to the middle temporal (MT) area, an early maturing dorsal stream cortical field, and which bypass the primary visual cortex (V1). These pathways are via the koniocellular layers of the lateral geniculate nucleus (LGN) and the medial portion of the inferior pulvinar (PIm). Both have been demonstrated in the adult nonhuman primate, but their influence during the maturation of the visual cortex is unknown. We used a combination of neural tracing and immunohistochemistry to follow the development of LGN and PIm inputs to area MT in the marmoset monkey. Our results revealed that the early maturation of area MT is likely due to the disynaptic retinopulvinar input and not the retinogeniculate input or the direct projection from V1. Furthermore, from soon after birth to adulthood, there was a dynamic shift in the ratio of input from these three structures to area MT, with an increasing dominance of the direct V1 afference.

背景与目标： : 灵长类视觉皮层和相关流的分层发展仍然是一个谜。尽管解剖学，生理学和心理学研究表明背侧 “where”/“how” 或运动皮质流的早期成熟，但对负责的电路知之甚少。已经研究了视网膜原肌纹状体途径的影响，但很少关注两个最近描述的双突触视网膜丘脑投射对中颞 (MT) 区域的作用，即早熟的背流皮层场，并且绕过了初级视觉皮层 (V1)。这些途径是通过外侧膝状核 (LGN) 和下牙髓 (PIm) 的内侧部分的细胞层。两者都已在成年非人类灵长类动物中得到证实，但它们在视觉皮层成熟过程中的影响尚不清楚。我们使用神经追踪和免疫组织化学的组合来跟踪LGN和PIm输入到mar猴中MT区域的发育。我们的结果表明，区域MT的早期成熟可能是由于非突触视网膜的输入，而不是视网膜的输入或来自v1的直接投影。此外，从出生后不久到成年，这三个结构的输入与区域MT的比率发生了动态变化，直接V1传入的优势越来越大。

BACKGROUND & AIMS: :Memory formation is hypothesized to involve the generation of event-specific neural activity patterns during learning and the subsequent spontaneous reactivation of these patterns. Here, we present evidence that these processes can also be observed in urethane-anesthetized rats and are enhanced by desynchronized brain state evoked by tail pinch, subcortical carbachol infusion, or systemic amphetamine administration. During desynchronization, we found that repeated tactile or auditory stimulation evoked unique sequential patterns of neural firing in somatosensory and auditory cortex and that these patterns then reoccurred during subsequent spontaneous activity, similar to what we have observed in awake animals. Furthermore, the formation of these patterns was blocked by an NMDA receptor antagonist, suggesting that the phenomenon depends on synaptic plasticity. These results suggest that anesthetized animals with a desynchronized brain state could serve as a convenient model for studying stimulus-induced plasticity to improve our understanding of memory formation and replay in the brain.

背景与目标： : 假设记忆形成涉及学习过程中事件特定的神经活动模式的产生以及这些模式随后的自发重新激活。在这里，我们提供的证据表明，这些过程也可以在氨基甲酸酯麻醉的大鼠中观察到，并且通过尾巴捏合，皮质下卡巴胆碱输注或全身苯丙胺给药引起的不同步的大脑状态而增强。在去同步化过程中，我们发现反复的触觉或听觉刺激诱发了体感和听觉皮层中神经放电的独特顺序模式，并且这些模式随后在随后的自发活动中再次发生，类似于我们在清醒动物中观察到的情况。此外，这些模式的形成被NMDA受体拮抗剂阻断，表明该现象取决于突触可塑性。这些结果表明，大脑状态不同步的麻醉动物可以作为研究刺激诱导的可塑性的方便模型，以提高我们对大脑中记忆形成和重放的理解。

BACKGROUND & AIMS: INTRODUCTION:Ovariectomy (OVX) results in bone loss caused by increased bone resorption. RANKL is an essential mediator of bone resorption. We examined whether the RANKL inhibitor osteoprotegerin (OPG) would preserve bone volume, density, and strength in OVX rats. MATERIALS AND METHODS:Rats were OVX or sham-operated at 3 mo of age. Sham controls were treated for 6 wk with vehicle (Veh, PBS). OVX rats were treated with Veh or human OPG-Fc (10 mg/kg, 2/wk). Serum RANKL and TRACP5b was measured by ELISA. BMD of lumbar vertebrae (L(1)-L(5)) and distal femur was measured by DXA. Right distal femurs were processed for bone histomorphometry. Left femurs and the fifth lumbar vertebra (L(5)) were analyzed by muCT and biomechanical testing, and L(6) was analyzed for ash weight. RESULTS:OVX was associated with significantly greater serum RANKL and osteoclast surface and with reduced areal and volumetric BMD. OPG markedly reduced osteoclast surface and serum TRACP5b while completely preventing OVX-associated bone loss in the lumbar vertebrae, distal femur, and femur neck. Vertebrae from OPG-treated rats had increased dry and ash weight, with no significant differences in tissue mineralization versus OVX controls. muCT showed that trabecular compartments in OVX-OPG rats had significantly greater bone volume fraction, vBMD, bone area, trabecular thickness, and number, whereas their cortical compartments had significantly greater bone area (p < 0.05 versus OVX-Veh). OPG improved cortical area in L(5) and the femur neck to levels that were significantly greater than OVX or sham controls (p < 0.05). Biomechanical testing of L(5) and femur necks showed significantly greater maximum load values in the OVX-OPG group (p < 0.05 versus OVX-Veh). Bone strength at both sites was linearly correlated with total bone area (r(2) = 0.54-0.74, p < 0.0001), which was also significantly increased by OPG (p < 0.05 versus OVX). CONCLUSIONS:OPG treatment prevented bone loss, preserved trabecular architecture, and increased cortical area and bone strength in OVX rats.

背景与目标：

BACKGROUND & AIMS: :We studied the involvement of deep cortical layer neurons in processing callosal information in the rat. We observed with electron microscopy that both parvalbumin (PV)-labeled profiles and unlabeled dendritic spines of deep cortical layer neurons receive synapses from the contralateral hemisphere. Stimulation of callosal fibers elicited monosynaptic excitatory postsynaptic currents in both layer VI pyramidal neurons and gamma-aminobutyric acidergic (GABAergic) interneurons immunopositive for the vesicular GABA transporter and PV. Pyramidal cells had intrinsic electrophysiological properties and synaptic responses with slow kinetics and a robust N-metyhl-D-aspartate (NMDA) component. In contrast, GABAergic interneurons had intrinsic membrane properties and synaptic responses with faster kinetics and a less pronounced NMDA component. Consistent with these results, the temporal integration of callosal input was effective over a significantly longer time window in pyramidal neurons compared with GABAergic interneurons. Interestingly, callosal stimulation did not evoke feedforward inhibition in all GABAergic interneurons and in the majority of pyramidal neurons tested. Furthermore, retrogradely labeled layer VI pyramidal neurons of the contralateral cortex responded monosynaptically to callosal stimulation, suggesting interconnectivity between callosally projecting neurons. The data show that pyramidal neurons and GABAergic interneurons of deep cortical layers receive interhemispheric information directly and have properties supporting their distinct roles.

背景与目标： : 我们研究了深皮质层神经元在处理大鼠call骨信息中的参与。我们用电子显微镜观察到，浅白蛋白 (PV) 标记的轮廓和深皮质层神经元的未标记的树突棘均从对侧半球接收突触。Call骨纤维的刺激在VI层锥体神经元和 γ-氨基丁酸 (GABA能) 中间神经元中均引起单突触兴奋性突触后电流，对囊泡GABA转运蛋白和PV免疫呈阳性。锥体细胞具有内在的电生理特性和突触反应，动力学缓慢，并且具有强大的N-metyhl-D-天冬氨酸 (NMDA) 成分。相反，gaba能中间神经元具有内在的膜特性和突触反应，其动力学更快，NMDA成分不那么明显。与这些结果一致，与gaba能中间神经元相比，在锥体神经元中，call骨输入的时间整合在明显更长的时间窗口内有效。有趣的是，在所有gaba能中间神经元和大多数测试的锥体神经元中，call刺激并未引起前馈抑制。此外，对侧皮层的逆行标记的第VI层锥体神经元对call骨刺激单突触反应，表明call骨投射神经元之间的相互连接。数据表明，皮层深层的锥体神经元和gaba能中间神经元直接接收半球间信息，并具有支持其独特作用的特性。

BACKGROUND & AIMS: :Using single and multiunit recordings in the striate cortex of alert macaque monkeys, we find that gamma-band (20-70 Hz) oscillations in neuronal firing are a prominent feature of V1 neuronal activity. The properties of this rhythmic activity are very similar to those previously observed in the cat. Gamma-band activity is strongly dependent on visual stimulation, largely absent during spontaneous activity and, under the conditions of our experiment, not time-locked to the vertical refresh of the computer monitor (80 Hz) used to present the stimuli. In our sample, 61% of multiunit activity (MUA) and 46% of single-unit activity (SUA) was significantly oscillatory, with mean frequencies of 48+/-9 and 42+/-13 Hz, respectively. Gamma-band activity was most likely to occur when cells were activated by their optimal stimuli, but still occurred, although less often and with lower amplitude, in response to nonoptimal stimuli. The frequency of gamma-band activity also reflected stimulus properties, with drifting gratings evoking higher-frequency oscillations than stationary gratings. As in the cat, the spike trains of single cells showing gamma-band oscillations often displayed a pattern of repetitive burst firing, with intraburst firing rates of 300-800 Hz. The overall similarity of rhythmic neuronal activity in the primary visual cortex of cats and monkeys suggests that the phenomenon is not species-specific. The stimulus-dependence of the rhythmic activity is consistent with a functional role in visual perception.

背景与目标： : 使用警报猕猴的纹状皮层中的单个和多单位记录，我们发现神经元放电中的伽玛带 (20-70Hz) 振荡是V1神经元活动的突出特征。这种节律活动的特性与以前在猫中观察到的非常相似。伽玛带活动在很大程度上取决于视觉刺激，在自发活动期间基本上不存在，并且在我们的实验条件下，与用于呈现刺激的计算机监视器 (80Hz) 的垂直刷新没有时间锁定。在我们的样本中，多单位活性61% (MUA) 和单单位活性46% (SUA) 显着振荡，平均频率分别为48/-9和42/-13Hz。当细胞被其最佳刺激激活时，最有可能发生 γ 带活性，但仍然发生，尽管频率较低且幅度较低，但响应于非最佳刺激。伽马带活动的频率也反映了刺激特性，漂移光栅比固定光栅引起更高频率的振荡。与cat一样，显示伽马带振荡的单个细胞的尖峰序列通常显示出重复爆发的模式，其内部发射速率为300-800Hz。猫和猴子初级视觉皮层中节律性神经元活动的总体相似性表明该现象不是特定于物种的。节律活动的刺激依赖性与视觉感知中的功能作用一致。

BACKGROUND & AIMS: :We evaluated the differences in strength of the associations of prevalent cardiovascular disease and lower extremity arterial atherosclerosis to common carotid intima-media thickness, assessed by near wall measurements only, by far wall measurements only, and by the average of near and far wall measurements. The study was based on data from 1500 participants of the Rotterdam Study, a single-center-population-based prospective follow-up study among 7983 subjects, aged 55 years or over. Comparison of the strength of the associations of near wall intima-media thickness and of combined near and far wall intima-media thickness to cardiovascular disease and lower extremity arterial atherosclerosis revealed significantly stronger associations compared to associations observed for far wall intima-media thickness, in particular for stroke and lower extremity arterial disease. We conclude that near wall common carotid intima-media thickness measurement provides at least as good an indicator of atherosclerosis elsewhere and of cardiovascular risk as the far wall intima-media thickness measurement.

背景与目标： : 我们评估了流行的心血管疾病和下肢动脉粥样硬化与颈总动脉内膜中层厚度的相关性的强度差异，仅通过近壁测量，仅通过远壁测量以及近壁和远壁测量的平均值来评估。该研究基于鹿特丹研究的1500名参与者的数据，该研究是一项基于单中心人群的前瞻性随访研究，涉及7983名年龄在55岁或以上的受试者。比较近壁内膜-中膜厚度以及近壁和远壁内膜-中膜厚度与心血管疾病和下肢动脉粥样硬化的相关性，发现与观察到的远壁内膜-中膜厚度的相关性相比，相关性明显更强，特别是对于中风和下肢动脉疾病。我们得出的结论是，近壁颈总动脉内膜中层厚度的测量至少与远壁内膜中层厚度的测量一样，可以很好地指示其他地方的动脉粥样硬化和心血管风险。

BACKGROUND & AIMS: :Biodegradable polymer microparticles are promising delivery depots for protein therapeutics due to their relatively simple fabrication and facile administration. Double-wall microspheres (DWMS) comprising a core and shell made of two distinct polymers may provide enhanced control of the drug release profiles. Using precision particle fabrication (PPF) technology, monodisperse DWMS were fabricated with model protein bovine serum albumin (BSA)-loaded poly(lactide-co-glycolide) (PLG) core and drug-free poly(d,l-lactic acid) (PDLL) shell of uniform thickness. Monolithic single-wall microspheres were also fabricated to mimic the BSA-loaded PLG core. Using ethyl acetate and dichloromethane as shell- and core-phase solvents, respectively, BSA was encapsulated selectively in the core region within DWMS with higher loading and encapsulation efficiency compared to using dichloromethane as core and shell solvents. BSA in vitro release rates were retarded by the presence of the drug-free PDLL shell. Moreover, increasing PDLL shell thickness resulted in decreasing BSA release rate. With a 14-μm thick PDLL shell, an extended period of constant-rate release was achieved.

背景与目标： : 由于其相对简单的制造和容易的给药，可生物降解的聚合物微粒是蛋白质治疗药物的有希望的递送库。包含由两种不同聚合物制成的核和壳的双壁微球 (DWMS) 可以提供对药物释放曲线的增强控制。使用精密颗粒制造 (PPF) 技术，用模型蛋白牛血清白蛋白 (BSA) 负载的聚 (丙交酯-共-乙交酯) (PLG) 核和无药聚 (d，l-乳酸) (PDLL) 制备单分散dwm。) 壳的厚度均匀。还制造了单片单壁微球以模拟装有BSA的PLG芯。分别使用乙酸乙酯和二氯甲烷作为壳和核相溶剂，与使用二氯甲烷作为核和壳溶剂相比，BSA以更高的负载和封装效率被选择性地封装在DWMS内的核心区域中。无药物PDLL壳的存在会延迟BSA的体外释放速率。此外，增加PDLL壳厚度导致BSA释放速率降低。使用14μm厚的PDLL壳，可以延长恒定速率释放时间。