Aesthetic judgment of architecture for Chinese observers.

Architects should consider the aesthetic experience of potential users when designing architectures. Previous studies have shown that subjective aesthetic judgment of architectures is influenced by structure features, and Western observers prefer structures that have curvilinear contours, high ceilings, and open space. The building styles, however, vary across cultures, and it remains unclear whether the preference for contours, ceiling height, and openness exist across cultures. To investigate this issue, this study analyzes the aesthetic judgment of Chinese observers, and the results demonstrate that Chinese observers also prefer high ceilings and open space. Preference for curvilinear contours, however, interacts with ceiling height and openness. Simple effect analysis reveals that Chinese observers prefer curvilinear contours only when the ceiling is low and the space is closed. In sum, these results suggest that preference for high ceilings and open space is robust for Chinese observers, but the preference for curvilinear contours is less reliable.

Numerical Study on Surface Roughness Measurement Based on Nonlinear Ultrasonics in Through-Transmission and Pulse-Echo Modes.

Ultrasonic is one of the well-known methods for surface roughness measurement, but small roughness will only lead to a subtle variation of transmission or reflection. To explore sensitive techniques for surfaces with small roughness, nonlinear ultrasonic measurement in through-transmission and pulse-echo modes was proposed and studied based on an effective unit-cell finite element (FE) model. Higher harmonic generation in solids was realized by applying the Murnaghan hyperelastic material model. This FE model was verified by comparing the absolute value of the nonlinearity parameter with the analytical solution. Then, random surfaces with different roughness values ranging from 0 µm to 200 µm were repeatedly generated and studied in the two modes. The through-transmission mode is very suitable to measure the surfaces with roughness as small as 3% of the wavelength. The pulse-echo mode is sensitive and effective to measure the surface roughness ranging from 0.78% to 5.47% of the wavelength. This study offers a potential nondestructive testing and monitoring method for the interfaces or inner surfaces of the in-service structures.

The Influence of Viewing Time and Color on Architectural Aesthetic Judgment.

Understanding the factors influencing the aesthetic experience of architectures is an important topic in empirical aesthetics. In this study, we examined the effect of three architectural factors, i.e., ceiling height, openness, and contour, on viewers' aesthetic appreciation through a series of experiments. In previous studies on architectural aesthetics, participants were usually asked to view an image of an architectural space for a few seconds. The long viewing time allows them to focus on different parts of the architecture and then make an aesthetic judgment. The long viewing time, however, also makes it difficult to obtain viewers' aesthetic scores for a large number of architectural spaces in a short period. In this study, we shortened the visual presentation time to 200 ms, which allowed the viewers to have only one fixation on the image, and asked the viewers to make an aesthetic judgment. It was found that the experiment with a 200-ms viewing time could establish how the three architectural factors influenced aesthetic judgment as well as previous experiments with a 3,000-ms viewing time, suggesting that aesthetic judgment could be made within one fixation. Additionally, we investigated the impact of color on architectural aesthetic judgment by presenting grayscale images. We found that the three architectural factors influenced aesthetic judgment in similar ways for both color and grayscale images. In summary, we found that color was not a main factor modulating viewers' architectural aesthetic judgments, and we also presented a way to quickly obtain aesthetic scores for architectural spaces.

Synaptotagmin-7 deficiency induces mania-like behavioral abnormalities through attenuating GluN2B activity.

Synaptotagmin-7 (Syt7) probably plays an important role in bipolar-like behavioral abnormalities in mice; however, the underlying mechanisms for this have remained elusive. Unlike antidepressants that cause mood overcorrection in bipolar depression, N-methyl-d-aspartate receptor (NMDAR)-targeted drugs show moderate clinical efficacy, for unexplained reasons. Here we identified Syt7 single nucleotide polymorphisms (SNPs) in patients with bipolar disorder and demonstrated that mice lacking Syt7 or expressing the SNPs showed GluN2B-NMDAR dysfunction, leading to antidepressant behavioral consequences and avoidance of overcorrection by NMDAR antagonists. In human induced pluripotent stem cell (iPSC)-derived and mouse hippocampal neurons, Syt7 and GluN2B-NMDARs were localized to the peripheral synaptic region, and Syt7 triggered multiple forms of glutamate release to efficiently activate the juxtaposed GluN2B-NMDARs. Thus, while Syt7 deficiency and SNPs induced GluN2B-NMDAR dysfunction in mice, patient iPSC-derived neurons showed Syt7 deficit-induced GluN2B-NMDAR hypoactivity that was rescued by Syt7 overexpression. Therefore, Syt7 deficits induced mania-like behaviors in mice by attenuating GluN2B activity, which enabled NMDAR antagonists to avoid mood overcorrection.

WHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes.

WHAMM, a member of the Wiskott-Aldrich syndrome protein (WASP) family, is an actin nucleation promoting factor (NPF) that also associates with membranes and microtubules. Here we report that WHAMM is required for autophagic lysosome reformation (ALR). WHAMM knockout causes impairment of autolysosome tubulation, which results in accumulation of enlarged autolysosomes during prolonged starvation. Mechanistically, WHAMM is recruited to the autolysosome membrane through its specific interaction with PI(4,5)P2. WHAMM then works as an NPF which promotes assembly of an actin scaffold on the surface of the autolysosome to promote autolysosome tubulation. Our study demonstrates an unexpected role of the actin scaffold in regulating autophagic lysosome reformation.

The Balance between Actin-Bundling Factors Controls Actin Architecture in Pollen Tubes.

How actin-bundling factors cooperatively regulate shank-localized actin bundles remains largely unexplored. Here we demonstrate that FIM5 and PLIM2a/PLIM2b decorate shank-localized actin bundles and that loss of function of PLIM2a and/or PLIM2b suppresses phenotypes associated with fim5 mutants. Specifically, knockout of PLIM2a and/or PLIM2b partially suppresses the disorganized actin bundle and intracellular trafficking phenotype in fim5 pollen tubes. PLIM2a/PLIM2b generates thick but loosely packed actin bundles, whereas FIM5 generates thin but tight actin bundles that tend to be cross-linked into networks in vitro. Furthermore, PLIM2a/PLIM2b and FIM5 compete for binding to actin filaments in vitro, and PLIM2a/PLIM2b decorate disorganized actin bundles in fim5 pollen tubes. These data together suggest that the disorganized actin bundles in fim5 mutants are at least partially due to gain of function of PLIM2a/PLIM2b. Our data suggest that the balance between FIM5 and PLIM2a/PLIM2b is crucial for the normal bundling and organization of shank-localized actin bundles in pollen tubes.

Structural Insights of WHAMM's Interaction with Microtubules by Cryo-EM.

WASP homolog associated with actin, membranes, and microtubules (WHAMM) is a vertebrate protein functioning in membrane tubulation for intracellular membrane trafficking and specific organelle formation. Composed of multiple domains, WHAMM can bind to membrane and microtubule (MT) and promote actin polymerization nucleation. Previous work revealed that WHAMM's activity to promote actin nucleation is repressed upon binding to MTs. Here, we discovered that WHAMM interacts with αß-tubulin through a small peptide motif within its MT-binding domain. We reconstructed a high-resolution structure of WHAMM's MT-binding motif (MBM) assembling around MTs using cryo-electron microscopy and verified it with chemical cross-linking and mass spectrometry analysis. We also detected a conformational switch of this motif between the non-MT-bound state and the MT-bound state. These discoveries provide new insights into the mechanism by which WHAMM coordinates actin and MT networks, the two major cytoskeletal systems involved in membrane trafficking and membrane remodeling.

Cataract-causing mutation R233H affects the stabilities of ßB1- and ßA3/ßB1-crystallins with different pH-dependence.

Disease-causing mutations can be stabilizing or destabilizing. Missense mutations of structural residues are generally destabilizing, while stabilizing mutations are usually linked to alterations in protein functions. Stabilizing mutations are rarely identified in mutations linked to congenital cataract, a disease caused by the opacification of the lens. In this research, we found that R233H mutation had little impact on ßB1-crystallin structure, solubility and thermal stability under neutral solution pH conditions. The mutation increased ßB1 stability against guanidine hydrochloride-induced denaturation, suggesting that Arg233 might be a functional residue. Further analysis indicated that the R233H mutation did not affect the formation of ßA3/ßB1 heteromer, but significantly reduced heteromer stability against heat- and guanidine hydrochloride-induced denaturation. The R233H mutation negatively affected the thermal stabilities and aggregatory propensities of ßB1 and ßA3/ßB1 with different pH-dependence, implying that the protonation of His side chains during acidification played a regulatory role in crystallin stability and aggregation. Molecular dynamic simulations indicated that Arg233 is one of the residues forming an inter-subunit ion-pairing network with intrinsically dynamic nature. Based on these observations, we proposed that the highly dynamic ion-pairing network contributed to the tradeoff among ßB1 solubility, stability, aggregatory propensity and function of protecting ßA3.

Cataract-linked mutation R188H promotes ßB2-crystallin aggregation and fibrillization during acid denaturation.

Cataract is characterized by the formation of light-scattering protein aggregates in the lens. ß/γ-Crystallins are the predominant structural proteins in the cytosol of lens fiber cells, and more than fifty ß/γ-crystallin mutations have been linked to autosomal dominant congenital cataract. However, the structural role of these mutations in the formation of the core structures of amorphous aggregates or amyloid-like fibrils has not been elucidated yet. In this research, we studied the effects of the V187M and R188H mutations on the aggregation and fibrillization of ßB2-crystallin during acid denaturation. The behavior of V187M was the same as the WT protein, suggesting that the residue at position 187 contributed little to the aggregation/fibrillization process. R188H promoted the formation of amorphous aggregates at pH above 3 and accelerated fibrillization at pH 3. The distinct behaviors of the mutants suggested that the residue at position 188 might play a regulatory role in ßB2-crystallin aggregation/fibrillization but not reside in the core of the aggregates/fibrils.

[Clinical analysis of prognostic factors for patients with gastrointestinal stromal tumors].

OBJECTIVE: To investigate the prognostic factors for patients with gastrointestinal stromal tumors (GIST). METHODS: From 2000 to 2003, clinical data of 41 cases with GIST were reviewed retrospectively. The clinicopathologic diagnosis was determined by immunochemistry. The relationships of the prognosis with mitotic counts, tumor size and location,range of tumor resection were analyzed. RESULTS: The patients with GIST had pathological section of high expression in CD117, CD34 and vimentin (92.7%, 82.9%, 78%, respectively). Patients with tumor location in intestine, tumor size > 5 cm,mitotic counts > 5/50HPF, incomplete resection had poorer outcome, compared with those with tumor location in stomach and colon,tumor size < or = 5 cm,mitotic counts < or = 5/50HPF and complete resection (all P< 0.05). CONCLUSION: Complete gross resection can improve prognosis for patients with GIST. Tumors with mitotic counts > or = 5/50HPF, tumor size more than 5 cm and tumor location in intestine are poor prognostic factors.

Study of hydrolytic kinetics of the hexachlorostannate anion by two-dimensional 119 Sn exchange spectroscopy.

Two-dimensional 119 Sn exchange spectroscopy was applied to study the hydrolytic kinetics of the hexachloro-stannate anion, SnCl6 2- . Two 119 Sn exchange spectra for SnCl4 · 5H2 O solutions with various HCl concentrations are presented. Magnetization exchanges, which are related to the hydrolysis processes, occur in the SnCl6 2- hydrolysis series. The exchange rate constants, the hydrolysis rate constants and the hydrolysis equilibrium constants were evaluated.