Biological Effects of Cyclin-Dependent Kinase Inhibitors Ribociclib,Palbociclib and Abemaciclib on Breast Cancer Bone Microenvironment

The CDK4/6 inhibitors (CDKi) palbociclib, ribociclib, and abemaciclib are currently approved in combination with anti-estrogen therapy for the treatment of advanced and/or metastatic hormone receptor-positive/HER2-neu-negative breast cancer patients. Given the high incidence of bone metastases in this population, we investigated and compared the potential effects of palbociclib, ribociclib, and abemaciclib on the breast cancer bone microenvironment. Primary osteoclasts (OCs) and osteoblasts (OBs) were obtained from human monocyte and mesenchymal stem cells, respectively. OC function was evaluated by tartrate-resistant acid phosphatase assay and real-time PCR; OB activity was assessed by an alizarin red assay. OB/breast cancer co-culture models were generated via the seeding of MCF-7 cells on a layer of OBs, and tumor cell proliferation was analyzed using flow cytometry. Here, we showed that ribociclib, palbociclib, and abemaciclib exerted similar inhibitory effects on the OC differentiation and expression of bone resorption markers without affecting OC viability. On the other hand, the three CDKi did not affect the ability of OB to produce bone matrix, even if the higher doses of palbociclib and abemaciclib reduced the OB viability. In OB/MCF-7 co-culture models, palbociclib demonstrated a lower anti-tumor effect than ribociclib and abemaciclib. Overall, our results revealed the direct effects of CDKi on the tumor bone microenvironment, highlighting differences potentially relevant for clinical practice.     

Cell Type-Specific Induction of Inflammation-Associated Genes in Crohn’s Disease and Colorectal Cancer

Based on the rapid increase in incidence of inflammatory bowel disease (IBD), the identification of susceptibility genes and cell populations contributing to this condition is essential. Previous studies suggested multiple genes associated with the susceptibility of IBD; however, due to the analysis of whole-tissue samples, the contribution of individual cell populations remains widely unresolved. Single-cell RNA sequencing (scRNA-seq) provides the opportunity to identify underlying cellular populations. We determined the enrichment of Crohn’s disease (CD)-induced genes in a publicly available Crohn’s disease scRNA-seq dataset and detected the strongest induction of these genes in innate lymphoid cells (ILC1), highly activated T cells and dendritic cells, pericytes and activated fibroblasts, as well as epithelial cells. Notably, these genes were highly enriched in IBD-associated neoplasia, as well as sporadic colorectal cancer (CRC). Indeed, the same six cell populations displayed an upregulation of CD-induced genes in a CRC scRNA-seq dataset. Finally, after integrating and harmonizing the CD and CRC scRNA-seq data, we demonstrated that these six cell types display a gradual increase in gene expression levels from a healthy state to an inflammatory and tumorous state. Together, we identified cell populations that specifically upregulate CD-induced genes in CD and CRC patients and could, therefore, contribute to inflammation-associated tumor development.     

The public health approach to youth violence and child maltreatment prevention at the Centers for Disease Control and Prevention.

Millions of people in the United States suffer the consequences of violence, including physical injuries, psychological trauma, and death. Solutions to violence have traditionally been reactive. Through the lens of the public health perspective, the Centers for Disease Control and Prevention (CDC) views violence as predictable based on various contributing factors, and thus as preventable. Within CDC, the Division of Violence Prevention (DVP) leads efforts to prevent injury, death, and disability, and to reduce the suffering and medical costs caused by violence. DVP employs a multidisciplinary, public health approach to identify factors associated with violence, and to develop, evaluate, and disseminate preventive interventions. Psychology is one discipline that has contributed to our approach. The authors present a series of violence prevention initiatives funded by the CDC that are framed within a public health perspective, with attention to the contributions of psychology to youth violence and child maltreatment prevention. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

ARCHER: an automated RF-IC Rx front-end circuit design tool

This paper presents a tool capable of automatically compiling the circuit of a direct-conversion receiver at the schematics level based on system specifications that include the frequency of operation, gain, noise figure, IIP2 and IIP3 linearity. The front-end of a direct-conversion receiver is built using inductive source degeneration (LSD) LNA and double-balanced source-degenerated Gilbert Cell mixers with charge injection. The tool uses power constrained noise and linearity optimization vector-space algorithms that automatically size the transistors, passive components, and find the optimum biasing points. The solution generated by the tool is automatically read by Agilent ADS where the blocks are easily fine-tuned and validated before layout. Case studies involving WiMAX, UMTS, GSM, Bluetooth and WLAN are presented to reveal the capabilities of the tool in reducing the design time.     

New advances in mitigating environmental impact of pipe-type cables

Through a comprehensive and aggressive research program, the Consolidated Edison Company of New York, Inc. (Con Edison) has designed, developed and installed several new products to address the environmental impact of leaked dielectric fluid from pipe-type cable systems. These include online leak detection, leak location, retractable flow direction indicator, full stop joints and transition joints. This paper describes the application of the aforementioned products on the Con Edison underground transmission system     

An asymmetric fingerprint matching algorithm for Java Card TM

We propose a light-weight fingerprint matching algorithm that can be executed inside the devices with a limited computational power. The algorithm is based on the minutiae local structures (the “neighborhoods”), that are invariant with respect to global transformations like translation and rotation. The match algorithm has been implemented inside a smartcard over the Java Card^TM platform, meeting the individual’s need for information privacy and overall authentication procedure security. The main characteristic of the algorithm is to have an asymmetric behavior, in respect to the execution time, between correct positive and negative matches. The performances in terms of authentication reliability and speed were tested on some databases from the Fingerprint Verification Competition 2002 and 2004 editions (FVC2002 and FVC2004). Moreover, our procedure showed better reliability when compared with a related algorithm on the same database. We can achieve a false acceptance rate (FAR) of 0.1%, a false rejection rate of about 6%, and from 0.3 to 8 s to match most of the finger pairs during the FAR tests.     

IDES: An Internet Distance Estimation Service for Large Networks

The responsiveness of networked applications is limited by communications delays, making network distance an important parameter in optimizing the choice of communications peers. Since accurate global snapshots are difficult and expensive to gather and maintain, it is desirable to use sampling techniques in the Internet to predict unknown network distances from a set of partially observed measurements. This paper makes three contributions. First, we present a model for representing and predicting distances in large-scale networks by matrix factorization which can model suboptimal and asymmetric routing policies, an improvement on previous approaches. Second, we describe two algorithms-singular value decomposition and non-negative matrix factorization-for representing a matrix of network distances as the product of two smaller matrices. Third, based on our model and algorithms, we have designed and implemented a scalable system-Internet Distance Estimation Service (IDES)-that predicts large numbers of network distances from limited samples of Internet measurements. Extensive simulations on real-world data sets show that IDES leads to more accurate, efficient and robust predictions of latencies in large-scale networks than existing approaches     

More on the psychology of false confessions.

Responds to comments by J. T. McCann (see record 1998-00122-001) and A. Reifman (see record 1998-00122-002) concerning S. M. Kassin's article (see record 1997-07781-003) on the psychology of false confessions. It is stated that these commentaries offer interesting perspectives with which to expand what is currently known about the psychology of confession evidence. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

On the solution of linear-programming problems with free (unrestricted) variables

This paper reviews the way free (unrestricted) variables are handled in the formulation and solution of linear-programming problems, and how such variables are processed in computerbased mathematical programming systems. Key theorems are proved that demonstrate the role of free variables in an optimal solution.     

Effects of task strain, social conflict, and emotional activation on ambulatory cardiovascular activity: Daily life consequences of recurring stress in a multiethnic adult sample.

Ambulatory blood pressure (ABP) may be an independent predictor of cardiovascular endpoints, but little is known about its psychosocial determinants. The acute effects of psychosocial processes on cardiovascular activity during daily life were examined by random-effects regression. Healthy adults (N?=?120) were monitored over a 6-day period with ABP monitors and computer-assisted self-report assessments. Task strain, social conflict, and emotional activation were rated following each ABP measurement, as were activity, posture, and other covariates. Results show that blood pressure) (BP) and heart rate (HR) were elevated during periods of emotional activation (high negative affect or high arousal). Diastolic BP was lower during periods involving high decisional control, and HR was lower during high-control, low-demand activities. There were substantial individual differences in the effects of psychosocial influences on ambulatory cardiovascular activity. Psychological factors are reliable determinants of ABP, which may account for the unique predictive value of ABP. (PsycINFO Database Record (c) 2010 APA, all rights reserved)