A chorea-acanthocytosis patient with novel mutations in the VPS13A gene without acanthocyte.

Chorea-acanthocytosis (ChAc) is a rare clinical genetic disorder of the nervous system, which is characterized by choreiform movement disorder, cognitive decline, and psychiatric disorders. ChAc is mostly diagnosed based on its typical clinical manifestations and the increased number of acanthocytes in peripheral blood smears. Here, we report a patient, who has the characteristic clinical manifestations of ChAc with limb choreiform movements, involuntary lip and tongue bites, seizures, and emotional instability. However, her blood smear was negative for acanthocytes with scanning electron microscopy. We later identified two novel pathogenic mutations in the patient's vacuolar protein sorting homolog 13 A (VPS13A) on chromosome 9q21 by targeted gene sequencing, and she was definitively diagnosed with "ChAc." After treatment with carbamazepine, haloperidol, the patient's symptoms gradually improved. We consider that an acanthocyte negative blood smear cannot rule out ChAC diagnosis, and genetic testing is the "gold standard" for the diagnosis. Through a review of previous research, it is rare for a patient to have a clear diagnosis of ChAc by genetic testing, but whose blood smear is negative for acanthocytes with electron microscopy. In addition, in this report, we discovered two novel pathogenic mutations, which have not been reported previously, and extended the genetic characteristics of ChAc.

Fabricating Well-Dispersed Poly(Vinylidene Fluoride)/Expanded Graphite Composites with High Thermal Conductivity by Melt Mixing with Maleic Anhydride Directly.

Maleic anhydride (MA) is introduced to fabricate poly(vinylidene fluoride)/expanded graphite (PVDF/EG) composites via one-step melt mixing. SEM micrographs and WAXD results have demonstrated that the addition of MA helps to exfoliate and disperse the EG well in the PVDF matrix by promoting the mobility of PVDF molecular chains and enhancing the interfacial adhesion between the EG layers and the PVDF. Thus, much higher thermal conductivities are obtained for the PVDF/MA/EG composites compared to the PVDF/EG composites that are lacking MA. For instance, The PVDF/MA/EG composite prepared with a mass ratio of 93:14:7 exhibits a high thermal conductivity of up to 0.73 W/mK. It is 32.7% higher than the thermal conductivity of the PVDF/EG composite that is prepared with a mass ratio of 93:7. Moreover, the introduction of MA leads to an increased melting peak temperature and crystallinity due to an increased nucleation site provided by the uniformly dispersed EG in the PVDF matrix. This study provides an efficient preparation method for PVDF/EG composites with a high thermal conductivity.

Phosphoinositide-Dependent Protein Kinases Regulate Cell Cycle Progression Through the SAD Kinase Cdr2 in Fission Yeast.

Aberration in the control of cell cycle contributes to the development and progression of many diseases including cancers. Ksg1 is a Schizosaccharomyces pombe fission yeast homolog of mammalian phosphoinositide-dependent protein kinase 1 (PDK1) which is regarded as a signaling hub for human tumorigenesis. A previous study reported that Ksg1 plays an important role in cell cycle progression, however, the underlying mechanism remains elusive. Our genomic library screen for novel elements involved in Ksg1 function identified two serine/threonine kinases, namely SAD family kinase Cdr2 and another PDK1 homolog Ppk21, as multicopy suppressors of the thermosensitive phenotype of ksg1-208 mutant. We found that overexpression of Ppk21 or Cdr2 recovered the defective cell cycle transition of ksg1-208 mutant. In addition, ksg1-208 Δppk21 cells showed more marked defects in cell cycle transition than each single mutant. Moreover, overexpression of Ppk21 failed to recover the thermosensitive phenotype of the ksg1-208 mutant when Cdr2 was lacking. Notably, the ksg1-208 mutation resulted in abnormal subcellular localization and decreased abundance of Cdr2, and Ppk21 deletion exacerbated the decreased abundance of Cdr2 in the ksg1-208 mutant. Intriguingly, expression of a mitotic inducer Cdc25 was significantly decreased in ksg1-208, Δppk21, or Δcdr2 cells, and overexpression of Ppk21 or Cdr2 partially recovered the decreased protein level of Cdc25 in the ksg1-208 mutant. Altogether, our findings indicated that Cdr2 is a novel downstream effector of PDK1 homologs Ksg1 and Ppk21, both of which cooperatively participate in regulating cell cycle progression, and Cdc25 is involved in this process in fission yeast.

Effect of KDP-Crystal Material Properties on Surface Morphology in Ultra-Precision Fly Cutting.

To study the effect of material properties on the surface morphology of potassium dihydrogen phosphate (KDP) crystals, an ultra-precision fly cutting machine tool with a single-point diamond tool was used to perform a cutting experiment on (100) crystal plane of the KDP crystal. The elastic modulus, shear modulus, hardness, and dislocation of KDP crystals are taken into the cutting force model by introducing the strain gradient plasticity theory. Since the size effect and dynamic response will affect the surface roughness during ultra-precision machining, the surface roughness of workpieces in ultra-precision fly cutting is hard to predict. Based on the previously established strain gradient plasticity theoretical model, cutting force model, and the dynamic characteristics of the ultra-precision fly cutting system, a surface morphology prediction model under the influence of KDP crystal material properties was established. Finally, the accuracy of the surface morphology prediction model was verified by ultra-precision fly cutting experiments, and identified the frequency range of the characteristic signal caused by the anisotropy of the KDP crystal from the frequency, thereby verifying the KDP crystal material properties has a significant effect on the surface of the machined workpiece roughness.

Experiments and identification of the unbalance of aerostatic guideways on the micro-scale.

In order to diagnose the unbalance of aerostatic guideways, displacement and acceleration sensors were used to measure the vibration signals of the unbalance of the aerostatic guideways caused by the gas fluctuation. The frequency characteristics for the unbalance of aerostatic guideways caused by gas fluctuation has been extracted from the measured signals by power spectral density, and the basic frequencies of the guideway system have been diagnosed according to spectral characteristics, in agreement with the results calculated by the corresponding motion equations and the finite element method.

DNA-conjugated quantum dot nanoprobe for high-sensitivity fluorescent detection of DNA and micro-RNA.

Herein, we report a convenient approach to developing quantum dots (QDs)-based nanosensors for DNA and micro-RNA (miRNA) detection. The DNA-QDs conjugate was prepared by a ligand-exchange method. Thiol-labeled ssDNA is directly attached to the QD surface, leading to highly water-dispersible nanoconjugates. The DNA-QDs conjugate has the advantages of the excellent optical properties of QDs and well-controlled recognition properties of DNA and can be used as a nanoprobe to construct a nanosensor for nucleic acid detection. With the addition of a target nucleic acid sequence, the fluorescence intensity of QDs was quenched by an organic quencher (BHQ2) via Förster resonance energy transfer. This nanosensor can detect as low as 1 fM DNA and 10 fM miRNA. Moreover, the QDs-based nanosensor exhibited excellent selectivity. It not only can effectively distinguish single-base-mismatched and random nucleic sequences but also can recognize pre-miRNA and mature miRNA. Therefore, the nanosensor has high application potential for disease diagnosis and biological analysis.

Carriage error identification based on cross-correlation analysis and wavelet transformation.

This paper proposes a novel method for identifying carriage errors. A general mathematical model of a guideway system is developed, based on the multi-body system method. Based on the proposed model, most error sources in the guideway system can be measured. The flatness of a workpiece measured by the PGI1240 profilometer is represented by a wavelet. Cross-correlation analysis performed to identify the error source of the carriage. The error model is developed based on experimental results on the low frequency components of the signals. With the use of wavelets, the identification precision of test signals is very high.