Evanescent single-molecule biosensing with quantum limited precision

Sensors that are able to detect and track single unlabelled biomolecules are an important tool both to understand biomolecular dynamics and interactions at nanoscale, and for medical diagnostics operating at their ultimate detection limits. Recently, exceptional sensitivity has been achieved using the strongly enhanced evanescent fields provided by optical microcavities and nano-sized plasmonic resonators. However, at high field intensities photodamage to the biological specimen becomes increasingly problematic. Here, we introduce an optical nanofibre based evanescent biosensor that operates at the fundamental precision limit introduced by quantisation of light. This allows a four order-of-magnitude reduction in optical intensity whilst maintaining state-of-the-art sensitivity. It enable quantum noise limited tracking of single biomolecules as small as 3.5 nm, and surface-molecule interactions to be monitored over extended periods. By achieving quantum noise limited precision, our approach provides a pathway towards quantum-enhanced single-molecule biosensors.Comment: 17 pages, 4 figures, supplementary informatio

Aspergillus fumigatus preexposure worsens pathology and improves control of Mycobacterium abscessus pulmonary infection in mice

ABSTRACT Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CF transmembrane conductance regulator (CFTR) gene. Mutations in this chloride channel lead to mucus accumulation, subsequent recurrent pulmonary infections, and inflammation, which, in turn, cause chronic lung disease and respiratory failure. Recently, rates of nontuberculous mycobacterial (NTM) infections in CF patients have been increasing. Of particular relevance is infection with Mycobacterium abscessus , which causes a serious, life-threatening disease and constitutes one of the most antibiotic-resistant NTM species. Interestingly, an increased prevalence of NTM infections is associated with worsening lung function in CF patients who are also coinfected with Aspergillus fumigatus . We established a new mouse model to investigate the relationship between A. fumigatus and M. abscessus pulmonary infections. In this model, animals exposed to A. fumigatus and coinfected with M. abscessus exhibited increased lung inflammation and decreased mycobacterial burden compared with those of mice infected with M. abscessus alone. This increased control of M. abscessus infection in coinfected mice was mucus independent but dependent on both transcription factors T-box 21 (Tbx21) and retinoic acid receptor (RAR)-related orphan receptor gamma t (RORγ-t), master regulators of type 1 and type 17 immune responses, respectively. These results implicate a role for both type 1 and type 17 responses in M. abscessus control in A. fumigatus -coinfected lungs. Our results demonstrate that A. fumigatus , an organism found commonly in CF patients with NTM infection, can worsen pulmonary inflammation and impact M. abscessus control in a mouse model. </jats:p

Faulty Behavior of Storage Elements and Its Effects on Sequential Circuits

It is often assumed that the faults in storage elements (SEs) can be modeled as output/input stuck-at faults of the element. They are implicitly considered equivalent to the stuck-at faults in the combinational logic surrounding the SE cells. Transistor-level faults in common SEs are examined here. A more accurate higher level fault model for elementary SEs that better represents the physical failures is presented. It is shown that a minimal (stuck-at) model may be adequate if only modest fault coverage is desired. The enhanced model includes some common fault behaviors of SEs that are not covered by the minimal fault model. These include data-feedthrough and clock-feedthrough behaviors, as well as problems with logic level retention. Fault models for complex SE cells can be obtained without a significant loss of information about the structure of the circuit. The detectability of feedthrough faults is considered

On Fault Modeling and Testing of Content-addressable Memories

Associative or content addressable memories can be used for many computing applications. This paper discusses fault modeling for the content addressable memory (CAM) chips. Detailed examination of a single CAM cell is presented. A functional fault model for a CAM architecture executing exact match derived from the single cell model is presented. An efficient testing strategy can be derived using the proposed fault mode

Design and Implementation of FPGA Configuration Logic Block Using Asynchronous Static NCL

This paper proposes the design of a FPGA configurable logic block (CLB) using asynchronous static NULL convention logic (NCL) Library. The proposed design uses three static LUT\u27s for implementing NCL logic functions. Each LUT can be configured to function as any one of the 27 fundamental NCL Static gates. The proposed CLB supports 10 inputs and three different outputs, each with resettable and inverting variations. The CLB has two modes: Configuration mode and operation mode. The static NCL FPGA CLB is simulated at the transistor level using the 1.8 V, 180 nm TSMC CMOS process

Detection of feed-through faults in CMOS storage elements

In testing sequential circuits, internal faults in the storage elements (SE's) are sometimes modeled as stuck-at faults in the combinational circuits surrounding the SE. The detection of some transistor-level faults that cannot be modeled as stuck-at are considered. These feed-through faults cause the cell to become either data-feed-through, which makes the cell combinational, or clock-feed-through, which causes the clock signal or its complement to appear at the output. Under such faults, the cell does not function as a memory element. Here it is shown that such faults may or may not be detected depending on delays involved. Conditions under which race-ahead occurs are identified

Data-Feedthrough Faults in Circuits using Unclocked Storage Elements

Some faults in storage elements (SEs) do not manifest as stuck-at-0/1 faults. These include data-feedthrough faults that cause the SE cell to exhibit combinational behaviour. The authors investigate the implications of such faults on the behaviour of circuits using unclocked SEs. It is shown that effects of data-feedthrough faults at the behavioural level are different from those due to stuck-at faults, and therefore tests generated for the latter may be inadequat

Articles problematics and specificity of creative style of Iraqi publicist Raphael Butti

The publicist and editor Raphael Butti was one of the pioneers of Iraqi social and political journalism. The study of his 400 articles between 1920 and 1956, have shown that the predominant direction of his work, the impulse for writing was the desire to promote and develop democratic institutions in Iraq. The subject matter of his publications was related to the need for freedom of choice, gender equality, freedom of speech and the press, and increasing the level of education of the individual. Applying the methods of problem-thematic, lexical-stylistic and comparative analysis of Rafael Butti's articles, the authors have revealed that almost all his articles are permeated by the theme of patriotism and reflect his broad outlook. At the same time, the relative paucity of the language and creative style of the Iraqi publicist was found, which is expressed, in particular, in the limited use of artistic expression. Rafael Butti focuses primarily on intellectual enlightenment, compensating for the lack of emotional messages with long analytical phrases, lengthy paragraphs, and lengthy headings