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The "singularity"--a future moment when artificial intelligence becomes equal to or surpasses human intelligence making them indistinguishable--can be challenged by philosophy. I present an ontology of life, the subject of bona fide intelligence, to interrogate what underlies human intelligence. I argue: 1) internal purposiveness is intrinsic to life, and 2) living beings are the only things not solely explicable by mechanical and chemical laws. I engage Hubert Dreyfus' critique of artificial reason, What Computers Still Can't Do, though his three criteria for human intelligence fall short due to his separating physical and phenomenological explanatory "worlds" arising in absence of an ontology of life. A further question concerns what instantiates human intelligence, which I later introduce as a promising point of departure. [ABSTRACT FROM AUTHOR]

The last decade has witnessed the breakthrough of deep neural networks (DNNs) in many fields. With the increasing depth of DNNs, hundreds of millions of multiply-and-accumulate (MAC) operations need to be executed. To accelerate such operations efficiently, analog in-memory computing platforms based on emerging devices, e.g., resistive RAM (RRAM), have been introduced. These acceleration platforms rely on analog properties of the devices and thus suffer from process variations. Consequently, weights in neural networks configured into these platforms can deviate from the nominal trained values, which may lead to feature errors and a significant degradation of the inference accuracy. Besides, additional HW aspects represent key controlling factors for such computing platforms, namely, the limited RRAM cell programmable conductance levels, which limits the number of bits stored in one RRAM cell, the ADC noise converting analog values to digital domain and the ADC power scaling with the number of bits of its output. To address these points, in this article, we propose a framework to enhance the robustness of neural networks under variations. First, an enhanced Lipschitz constant regularization is adopted during neural network training to suppress the amplification of errors propagated through network layers. Additionally, the quantization setting of a NN model is optimized considering robustness against weight variations and total ADC power consumption. Afterward, error compensation is introduced at necessary locations determined by reinforcement learning (RL) to rescue the feature maps with remaining errors. Experimental results demonstrate that inference accuracy of neural networks can be recovered from as low as 1.69% under variations back to more than 95% of their original accuracy at the highest level of variations and reducing total ADC power consumption by 55% while the training and hardware cost are negligible.

A large number of multiply-accumulate operations and memory accesses required in deep convolutional neural networks (DCNN) leads to high latency and energy consumption (EC), that hinder their further applications. Dataflow-based acceleration schemes reduce memory accesses by leveraging reusable data in DCNNs. Row Stationary (RS) dataflow is a more advanced dataflow. In the convolutional layer acceleration of RS dataflow, the flexibility of mapping from logical processing element (LPE) sets to physical PE sets is relatively poor. The utilization of processing elements (PEs) is low. In this article, a novel mapping strategy based on genetic algorithm (GAMS) with the goal of optimizing EC is proposed. GAMS is designed to address the energy inefficiencies faced when mapping RS dataflow. A 3D hybrid optical-electrical Network-on-Chip (3DHOENoC) is proposed to further improve the communication efficiency, energy efficiency and the processing speed of DCNN. Simulation and evaluation results show that GAMS can achieve better mapping flexibility, higher PEs utilization and 15.9% improvement of execution speed on average. In addition, the execution time (ET) performance of processing the DCNN can be further improved by adopting the 3DHOENoC architecture with better communication parallelism.

•Vitamin D deficiency is pervasive and problematic in HSCT; repletion is poorly tolerated and rapidly catabolized.•We show marked, rapid, sustained improvement in vitamin D levels for 20 patients with novel, OTF cholecalciferol formulation.

A fast and efficient search function across the database has been a core component for a number of data-intensive tasks in machine learning, IoT applications, and inference. However, the conventional digital machines implementing the search functionality with repetitive arithmetic operations suffer from the energy efficiency and performance degradation due to the significant data transfer between the storage and processing units in the Von Neumann architecture. Ternary content addressable memories (TCAMs) are an essential hardware form of computing-in-memory (CiM) designs that aim to overcome the data transfer bottlenecks by implementing the parallel associative search function within the memory blocks. While most state-of-the-art TCAM designs focus on improving the information density by harnessing compact nonvolatile memories (NVMs), little efforts have been spent on optimizing the energy efficiency of the NVM-based TCAM. In this article, by exploiting the ferroelectric FET (FeFET) as a representative NVM, we propose an NOR-type 2FeFET-1T and an NAND-type 2FeFET-2T TCAM designs that enable highly energy-efficient associative search by reducing the associated precharge overheads. We then propose a hybrid ferroelectric NAND-NOR (HFNN) TCAM design to further improve the energy efficiency. An HFNN-based segmented architecture is proposed to reduce the search delay and energy by search operation pipeline. Evaluation results suggest that the proposed 2FeFET-1T, 2FeFET-2T and HFNN TCAM design consume $3.03\times $ , $8.08\times $ , and $226.92\times $ less search energy than the conventional 16T complementary metal oxide semiconductor (CMOS) TCAM, respectively. Application benchmarking shows that our proposed 2FeFET-1T/2FeFET-2T/HFNN TCAM can save, on average, 45.2%/50.6%/57.5% the GPU energy consumption as compared to the conventional GPU.

Memristor crossbar arrays are considered to be a promising platform for neuromorphic computing. To deploy a trained neural network (NN) model on memristor crossbars, memristors need to be programmed to the corresponding weight values. In fact, due to device-based process variation and noise, deviations of the stored weights from the trained weights are inevitable, thereby causing the degradation of the actual inference performance. This article proposes a unified Bayesian inference-based framework, BRoCoM, which connects device nonidealities and algorithmic training together for robust computing on memristor crossbars. BRoCoM is able to incorporate different levels of nonidealities into prior weight distribution, and transform robustness optimization to Bayesian NN (BNN) training, the weights of NNs are optimized to accommodate uncertainties and minimize inference degradation. Experimental results confirm the capability of the proposed BRoCoM to achieve stable inference performance while tolerating the nonideal effects of process variation and noise.

Oxysterols (OHCs) are hydroxylated cholesterol metabolites that play ubiquitous roles in health and disease. Due to the non-covalent nature of their interactions and their unique partitioning in membranes, the analysis of live-cell, proteome-wide interactions of OHCs remains an unmet challenge. Here, we present a structurally precise chemoproteomics probe for the biologically active molecule 20(S)-hydroxycholesterol (20(S)-OHC) and provide a map of its proteome-wide targets in the membranes of living cells. Our target catalog consolidates diverse OHC ontologies and demonstrates that OHC-interacting proteins cluster with specific processes in immune response and cancer. Competition experiments reveal that 20(S)-OHC is a chemo-, regio- and stereoselective ligand for the protein transmembrane protein 97 (Tmem97/the σ2 receptor), enabling us to reconstruct the 20(S)-OHC–Tmem97 binding site. Our results demonstrate that multiplexed, quantitative analysis of cellular target engagement can expose new dimensions of metabolite activity and identify actionable targets for molecular therapy.

Aberrations in the Hedgehog (Hh) signaling pathway are responsible for a broad range of human cancers, yet only a subset rely on the activity of the clinical target, Smoothened (Smo). Emerging cases of cancers that are insensitive to Smo-targeting drugs demand new therapeutic targets and agents for inhibition. As such, we sought to pursue a recently discovered connection between the Hedgehog pathway transcription factors, the glioma-associated oncogene homologues (Glis), and protein kinase C (PKC) isozymes. Here, we report our assessment of a structurally diverse library of PKC effectors for their influence on Gli function. Using cell lines that employ distinct mechanisms of Gli activation up- and downstream of Smo, we identify a PKC effector that acts as a nanomolar Gli antagonist downstream of Smo through a mitogen-activated protein kinase kinase (MEK)-independent mechanism. This agent provides a unique tool to illuminate crosstalk between PKC isozymes and Hh signaling and new opportunities for therapeutic intervention in Hh pathway-dependent cancers.

Objectives:To identify risk factors and evaluate the impact of various facial fractures and reconstruction surgeries on postoperative weight change. Methods:Retrospective, monocentric study was performed at a tertiary care center. Medical history, type and mechanism of fracture, operative factors, and postoperative weights at follow-up appointments for 145 adult patients undergoing surgical repair for maxillofacial fractures were collected. Further information was obtained on postoperative diet and whether patients received maxillomandibular fixation (MMF). Univariate and multivariate analyses were utilized to evaluate effects of surgical reconstruction after facial trauma on postoperative weight loss. Results:Patients lost 3.2 ± 4.9 kg (95% confidence interval = 2.7-4.1, P< .0001) on average, with maximum loss between date of surgery and first follow-up. Univariate analysis demonstrated that intensive care unit admission (5.9 kg, SD 5.4, P= .001), nasogastric tube placement (5.1 kg, SD 4.6, P= .012), and MMF (4.4 kg, SD 5.4, P< .0001) were associated with more severe weight loss. Multivariate analyses showed that only MMF remained a significant risk factor for increased weight loss (avg. 6.0, standard error 1.93, tvalue 3.11, P= .0024). Conclusions:We report significant weight loss following facial trauma and reconstruction, which emphasizes the need to perform further studies on nutrition protocols for this patient population to optimize wound healing.

This article will identify common causes of pain following traumatic brain injury (TBI), discuss current treatment strategies for these complaints, and help tailor treatments for both acute and chronic settings. We will also briefly discuss primary and secondary headache disorders, followed by common secondary pain disorders that may be related to trauma.

Prednisone is an anti-inflammatory glucocorticoid (GC) that is cytotoxic for normal and malignant B cells and, on this basis, has long been included in combination chemotherapies to treat aggressive B-cell lymphomas, including diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL). GCs act by binding to the glucocorticoid receptor (GR; NR3C1), a ligand-induced transcription factor. The transcriptional response to GCs can vary significantly due to the variation in expression levels of GR cofactors and chromatin landscapes in different cell types. The mechanisms by which GCs kill malignant lymphoma cells are largely unknown, prompting us to search for new targets of GC action with the hypothesis that GCs may inhibit key survival pathways in lymphomas.

Pacific Island Countries (PICs) face unique challenges in providing surgical care. We assessed the surgical care capacity of five PICs to inform the development of National Surgical, Obstetric and Anaesthesia Plans (NSOAP).

Yidian(, a little) in Chinese is commonly considered an indefinite and under-specific quantifier. This study provides some rethinking of Yidianthrough the lens of elasticity theory, based on real-life data from TV discussions. Elasticity theory offers new insights on the study of yidian,arguing that Yidianis both an elastic quantifier and a qualifier. The findings show that while Yidianindicates a small quantity and lesser degree, it is elastic and functions multi-dimensionally from mitigating to boosting. The frequency distributions of three pragmatic functions (just-right which is unmarked, mitigating and boosting which are marked) suggest that Yidianis used more for informational than interpersonal and political purposes. In a positive utterance Yidiantends to be a mitigator, but in negation it is a booster. The manifestation of elasticity is in Yidian’s fluidity, stretchability and strategy, enabling it to stretch to suit various contexts and making it a powerful ‘little’ word that performs a ‘big’ role in communication.

The identification of clinically significant genes recurrently mutated in myeloid malignancies necessitates expanding diagnostic testing with higher throughput, such as targeted next-generation sequencing. We present validation of the Thermo Fisher Oncomine Myeloid Next-Generation Sequencing Panel (OMP), targeting 40 genes and 29 fusion drivers recurrently mutated in myeloid malignancies. The study includes data from a sample exchange between two Canadian hospitals demonstrating high concordance for detection of DNA and RNA aberrations. Clinical validation demonstrates high accuracy, sensitivity, and specificity of the OMP, with a lower limit of detection of 5% for single-nucleotide variants and 10% for insertions/deletions. Prospective sequencing was performed for 187 samples from 168 unique patients presenting with suspected or confirmed myeloid malignancy and other hematological conditions to assess clinical impact of identifying variants. Of detected variants, 48% facilitated or clarified diagnoses, 29% affected prognoses, and 25% had the potential to influence clinical management. Of note, OMP was essential to identifying patients with premalignant clonal states likely contributing to cytopenias. We also found that the detection of even a single variant by the OMP assay, versus 0 variants, was predictive of overall survival, independent of age, sex, or diagnosis (P = 0.03). This study demonstrates that molecular profiling of myeloid malignancies with the OMP represents a promising strategy to advance molecular diagnostics.

Cardiopulmonary telerehabilitation is a safe and effective alternative to traditional center-based rehabilitation. It offers a sustainable solution to more conveniently meet the needs of patients with acute or chronic, pre-existing or newly acquired, cardiopulmonary diseases. To maximize success, programs should prioritize basic, safe and timely care options over comprehensive or complex approaches. The future should incorporate new strategies learned during a global pandemic as well as harness the power of information and communication technology to provide evidence-based patient-centered care. This review highlights clinical considerations, current evidence, recommendations and future directions of cardiopulmonary telerehabilitation.

Previous studies linked infection by Chlamydia psittaci to ocular adnexal lymphomas in Italian patients (Ferreri et al., JNCI 2004). Patients treated with doxycycline to eradicate the organism have demonstrated disease regression (Ferreri et al., J. Clin Oncol, 2005). To assess whether Chlamydia psittaci is associated with ocular adnexal lymphomas in a North American population, we studied 24 ocular adnexal lymphoma biopsy specimens from adults, 16 control lymphoma specimens from patients with systemic lymphomas not involving the ocular adnexa and five benign control ocular tissue samples. There were fifteen MALT, five diffuse, large B-cell, three follicular, and one mantle cell lymphoma specimens. The presence of Chlamydia psittaci DNA was investigated by PCR in each group. DNA was isolated from sections of formalin-fixed, paraffin-embedded tissue. Two different assays were utilized: 1) a previously published conventional PCR/gel based assay targeting a 111 bp fragment of the 16S gene [Madico, J. Clin Micro, 2000] and 2) a realtime PCR assay amplifying a 148 bp portion of the 16S gene with detection via a specific fluorescent probe. Amplification was carried out to 60 cycles. Positive controls consisted of isolated DNA from Chlamydia psittaci strain VS1, CP3, and FP. A human DNA internal control was utilized to assess DNA quality and amplification success. Both assays detected Chlamydia psittaci DNA from isolated strains. All patient samples in all categories yielded negative results using both assays. Thus, we could not confirm that Chlamydia psittaci is associated with ocular adnexal lymphomas in our patient population. Differences in the prevalence of Chlamydia psittaci infection in North America and Europe or technical differences in application of the assays may underlie the differences in our findings when compared to the Italian series. Confirmation with larger numbers of specimens is required.

Previous studies linked infection by Chlamydia psittacito ocular adnexal lymphomas in Italian patients (Ferreri et al., JNCI 2004). Patients treated with doxycycline to eradicate the organism have demonstrated disease regression (Ferreri et al., J. Clin Oncol, 2005). To assess whether Chlamydia psittaciis associated with ocular adnexal lymphomas in a North American population, we studied 24 ocular adnexal lymphoma biopsy specimens from adults, 16 control lymphoma specimens from patients with systemic lymphomas not involving the ocular adnexa and five benign control ocular tissue samples. There were fifteen MALT, five diffuse, large B-cell, three follicular, and one mantle cell lymphoma specimens. The presence of Chlamydia psittaciDNA was investigated by PCR in each group. DNA was isolated from sections of formalin-fixed, paraffin-embedded tissue. Two different assays were utilized: 1) a previously published conventional PCR/gel based assay targeting a 111 bp fragment of the 16S gene [Madico, J. Clin Micro, 2000] and 2) a realtime PCR assay amplifying a 148 bp portion of the 16S gene with detection via a specific fluorescent probe. Amplification was carried out to 60 cycles. Positive controls consisted of isolated DNA from Chlamydia psittacistrain VS1, CP3, and FP. A human DNA internal control was utilized to assess DNA quality and amplification success. Both assays detected Chlamydia psittaciDNA from isolated strains. All patient samples in all categories yielded negative results using both assays. Thus, we could not confirm that Chlamydia psittaciis associated with ocular adnexal lymphomas in our patient population. Differences in the prevalence of Chlamydia psittaciinfection in North America and Europe or technical differences in application of the assays may underlie the differences in our findings when compared to the Italian series. Confirmation with larger numbers of specimens is required.