Scalar Quantization as Sparse Least Square Optimization

Quantization can be used to form new vectors/matrices with shared values close to the original. In recent years, the popularity of scalar quantization for value-sharing applications has been soaring as it has been found huge utilities in reducing the complexity of neural networks. Existing clustering-based quantization techniques, while being well-developed, have multiple drawbacks including the dependency of the random seed, empty or out-of-the-range clusters, and high time complexity for a large number of clusters. To overcome these problems, in this paper, the problem of scalar quantization is examined from a new perspective, namely sparse least square optimization. Specifically, inspired by the property of sparse least square regression, several quantization algorithms based on $l_1$ least square are proposed. In addition, similar schemes with $l_1 + l_2$ and $l_0$ regularization are proposed. Furthermore, to compute quantization results with a given amount of values/clusters, this paper designed an iterative method and a clustering-based method, and both of them are built on sparse least square. The paper shows that the latter method is mathematically equivalent to an improved version of k-means clustering-based quantization algorithm, although the two algorithms originated from different intuitions. The algorithms proposed were tested with three types of data and their computational performances, including information loss, time consumption, and the distribution of the values of the sparse vectors, were compared and analyzed. The paper offers a new perspective to probe the area of quantization, and the algorithms proposed can outperform existing methods especially under some bit-width reduction scenarios, when the required post-quantization resolution (number of values) is not significantly lower than the original number

Clinical and immunological features of an APLAID patient caused by a novel mutation in PLCG2

BackgroundThe APLAID syndrome is a rare primary immunodeficiency caused by gain-of-function mutations in the PLCG2 gene. We present a 7-year-old APLAID patient who has recurrent blistering skin lesions, skin infections in the perineum, a rectal perineal fistula, and inflammatory bowel disease.MethodsTo determine the genetic cause of our patient, WES and bioinformatics analysis were performed. Flow cytometry was used for phenotyping immune cell populations in peripheral blood. Cytokines released into plasma were analyzed using protein chip technology. The PBMCs of patient and a healthy child were subjected to single-cell RNA-sequencing analysis.ResultsThe patient carried a novel de novo missense mutation c.2534T>C in exon 24 of the PLCG2 gene that causes a leucine to serine amino acid substitution (p.Leu845Ser). Bioinformatics analysis revealed that this mutation had a negative impact on the structure of the PLCγ2 protein, which is highly conserved in many other species. Immunophenotyping by flow cytometry revealed that in addition to the typical decrease in circulating memory B cells, the levels of myeloid dendritic cells (mDCs) in the children’s peripheral blood were significantly lower, as were the CD4+ effector T cells induced by their activation. Single-cell sequencing revealed that the proportion of different types of cells in the peripheral blood of the APLAID patient changed.ConclusionsWe present the first case of APLAID with severely reduced myeloid dendritic cells carrying a novel PLCG2 mutation, and conducted a comprehensive analysis of immunological features in the ALPAID patient, which has not been mentioned in previous reports. This study expands the spectrum of APLAID-associated immunophenotype and genotype. The detailed immune analyses in this patient may provide a basis for the development of targeted therapies for this severe autoinflammatory disease

4-[Bis(1H-indol-3-yl)meth­yl]benzonitrile

In the title mol­ecule, C24H17N3, the didhedral angles formed by the mean planes of the indole ring systems and the benzene ring are 86.44 (7) and 86.96 (7)°. The dihedral angle between the two indole ring systems is 72.08 (6)°. In the crystal, inter­molecular bifurcated (N—H)2⋯N hydrogen bonds link mol­ecules into sheets lying parallel to (010)

Association between gut microbiota, microbial network, and immunity in pregnancy with a focus on specific bacterial clusters

BackgroundThe community characteristics of the gut microbiota are not well defined and are not as widely studied as the functions of individual bacteria. This study aims to investigate the community composition of intestinal flora in women of childbearing age by conducting cluster analysis of gut microbiota and analyzing the relationship between different clusters and immune status.MethodsA total of 45 women of childbearing age were recruited in the study, including 15 non-pregnant women and 30 women in late pregnancy, and stool samples were collected twice during the third trimester, specifically at 32 weeks and at full term. The gut microbiota data was analyzed using 16S rRNA amplicon sequencing. Partitioning Around Medoids algorithm was employed to assess microbial clustering patterns. Microbial network for each cluster was performed and plasm cytokines were measured to analyze the relationship between specific genera and immune state in clusters.ResultsThere were three distinct clusters of intestinal community composition in women of childbearing age. Cluster 1 (PAM_1) was characterized by a high abundance of Bacteroides, while cluster 2 (PAM_2) showed higher levels of Bifidobacterium and Blautia, along with a significantly increased Firmicutes to Bacteroidota ratio. Cluster 3 (PAM_3) displayed a high abundance of Escherichia-shigella. PAM_1 was the most dominant cluster in non-pregnant women, and this dominant cluster was also one of the main in late pregnancy. At full term, the majority of subjects retained the same cluster as at 32 weeks, while a few experienced a shift. The microbial correlation networks differed across the three clusters, with PAM_1 exhibiting higher modularity and fewer connections. Analysis of the correlation between genera and plasma cytokines showed significant differences in their associations with cytokines between pregnancy and nonpregnancy within the same cluster, and the same genera had different effects in different clusters.ConclusionWomen of childbearing age exhibit three distribution patterns of gut microbiota, and the intestinal clusters reshaped during late pregnancy in a small population. Different clusters may have diverse immunomodulatory effects in different physiological states. When studying the gut microbiome during pregnancy, it is crucial to consider the cluster differences within healthy women

Pyrimido[4,5‐ d ]pyrimidin‐4(1 H )‐one Derivatives as Selective Inhibitors of EGFR Threonine 790 to Methionine 790 (T790M) Mutants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99681/1/8387_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99681/2/anie_201302313_sm_miscellaneous_information.pd

Pyrimido[4,5‐ d ]pyrimidin‐4(1 H )‐one Derivatives as Selective Inhibitors of EGFR Threonine 790 to Methionine 790 (T790M) Mutants

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99673/1/8545_ftp.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/99673/2/ange_201302313_sm_miscellaneous_information.pd

Enzyme Kinetics Studies of Nucleoside Diphosphate Kinase in Human Erythrocytes and Frequency Distribution in Healthy Subjects and Transplant Recipients in Chinese Han Population

ABSTRACT Nucleoside diphosphate kinase (NDPK), as a house-keeping protein, involves in various molecular processes including signal transduction, energy and drug metabolism. The main objective was to investigate NDPK kinetics in human erythrocytes and to monitor the frequency distribution of NDPK activity levels in Chinese healthy subjects and transplant recipients. METHODS: NDPK activity in erythrocytes was detected by a validated ion-pair high-performance liquid chromatogram method. NDPK kinetics studies were carried out systematically. NDPK activity levels were determined in 500 healthy subjects, 250 kidney and 250 liver transplant recipients in Chinese Han population. RESULTS: Thermal and pH stability studies indicated NDPK was relatively stable at temperature 30-45ºC and pH 6.0-9.0. In substrate dependency study, the apparent Michaelis-Menten constant (K m ) and maximum velocity of enzymatic reaction (V max ) increased with concentration of substrates. Meanwhile, in product inhibition study, with the increasing concentration of dATP, the V max of dADP decreased with constant K m and K m of dGTP increased with constant V max . NDPK activity levels revealed a 7-fold variability and were not normally distributed in all groups. NDPK activity levels were significantly (P<0.05) higher in transplant group than those in health group. Additionally, much higher NDPK activity levels had been shown (P<0.001) in liver transplant recipients when compared to kidney transplant cases. CONCLUSIONS: NDPK kinetics studies indicated substrate dependency of NDPK and a "ping-pong" mechanism for production inhibition. Skewness distributions of NDPK activity levels were shown in the study population. The transplant recipients showed higher NDPK activity levels when compared to healthy subjects

Factors affecting the early establishment of neonatal intestinal flora and its intervention measures

In recent years, it has become evident that early-life intestinal flora plays a pivotal role in determining human health. Consequently, it is imperative to explore the establishment of neonatal intestinal flora and its influencing factors. Early neonatal intestinal flora is influenced by a multitude of factors, including maternal and infant-related factors, as well as external environment. This review summarizes the colonization mechanism of intestinal flora in the early life of newborns and discussed their influence on the establishment of neonatal intestinal flora, taking into account factors such as delivery mode, gestational age and feeding mode. Additionally, this review delves into the natural or artificial reconstruction of intestinal flora colonization defects in infants born via cesarean section and premature infants, with the goal of establishing a theoretical foundation for preventing and treating issues related to neonatal intestinal flora colonization and associated diseases

Disrupted Cerebellar Connectivity With the Central Executive Network and the Default-Mode Network in Unmedicated Bipolar II Disorder

Objective: Bipolar disorder (BD) is a common psychiatric disease. Although structural and functional abnormalities of the cerebellum in BD patients have been reported by recent neuroimaging studies, the cerebellar-cerebral functional connectivity (FC) has not yet been examined. The present study aims to investigate the FC between the cerebellum and cerebrum, particularly the central executive network (CEN) and the default-mode network (DMN) in bipolar II disorder (BD II).Methods: Ninety-four patients with unmedicated BD II depression and 100 healthy controls (HCs) underwent the resting-state functional magnetic resonance imaging. Seed-based connectivity analyses were performed using cerebellar seeds previously identified as being involved in the CEN (bilateral Crus Ia) and DMN (bilateral Crus Ib).Results: Compared with HCs, BD II depression patients appeared decreased FC in the right Crus Ia-left dorsal lateral prefrontal cortex (dlPFC) and -left anterior cingulate cortex (ACC), the right Crus Ib-left medial prefrontal cortex (mPFC), -left middle temporal gyrus (MTG), and -left inferior temporal gyrus (ITG). No altered FC between the left Crus Ia or Crus Ib and the cerebral regions was found.Conclusions: Patients with BD II depression showed disrupted FC between the cerebellum and the CEN (mainly in the left dlPFC and ACC) and DMN (mainly in the left mPFC and temporal lobe), suggesting the significant role of the cerebellum-CEN and -DMN connectivity in the pathogenesis of BD