Multiple sequence alignment

Multiple sequence alignment

Multiple sequence alignment (MSA) is the process or the result of sequence alignment of three or more biological sequences, generally protein, DNA, or RNA. These alignments are used to infer evolutionary relationships via phylogenetic analysis and can highlight homologous features between sequences. Alignments highlight mutation events such as point mutations (single amino acid or nucleotide changes), insertion mutations and deletion mutations, and alignments are used to assess sequence conservation and infer the presence and activity of protein domains, tertiary structures, secondary structures, and individual amino acids or nucleotides. Multiple sequence alignments require more sophisticated methodologies than pairwise alignments, as they are more computationally complex. Most multiple sequence alignment programs use heuristic methods rather than global optimization because identifying the optimal alignment between more than a few sequences of moderate length is prohibitively computationally expensive. However, heuristic methods generally cannot guarantee high-quality solutions and have been shown to fail to yield near-optimal solutions on benchmark test cases. == Problem statement == Given m {\displaystyle m} sequences S i {\displaystyle S_{i}} , i = 1 , ⋯ , m {\displaystyle i=1,\cdots ,m} similar to the form below: S := { S 1 = ( S 11 , S 12 , … , S 1 n 1 ) S 2 = ( S 21 , S 22 , ⋯ , S 2 n 2 ) ⋮ S m = ( S m 1 , S m 2 , … , S m n m ) {\displaystyle S:={\begin{cases}S_{1}=(S_{11},S_{12},\ldots ,S_{1n_{1}})\\S_{2}=(S_{21},S_{22},\cdots ,S_{2n_{2}})\\\,\,\,\,\,\,\,\,\,\,\vdots \\S_{m}=(S_{m1},S_{m2},\ldots ,S_{mn_{m}})\end{cases}}} A multiple sequence alignment is taken of this set of sequences S {\displaystyle S} by inserting any amount of gaps needed into each of the S i {\displaystyle S_{i}} sequences of S {\displaystyle S} until the modified sequences, S i ′ {\displaystyle S'_{i}} , all conform to length L ≥ max { n i ∣ i = 1 , … , m } {\displaystyle L\geq \max\{n_{i}\mid i=1,\ldots ,m\}} and no values in the sequences of S {\displaystyle S} of the same column consists of only gaps. The mathematical form of an MSA of the above sequence set is shown below: S ′ := { S 1 ′ = ( S 11 ′ , S 12 ′ , … , S 1 L ′ ) S 2 ′ = ( S 21 ′ , S 22 ′ , … , S 2 L ′ ) ⋮ S m ′ = ( S m 1 ′ , S m 2 ′ , … , S m L ′ ) {\displaystyle S':={\begin{cases}S'_{1}=(S'_{11},S'_{12},\ldots ,S'_{1L})\\S'_{2}=(S'_{21},S'_{22},\ldots ,S'_{2L})\\\,\,\,\,\,\,\,\,\,\,\vdots \\S'_{m}=(S'_{m1},S'_{m2},\ldots ,S'_{mL})\end{cases}}} To return from each particular sequence S i ′ {\displaystyle S'_{i}} to S i {\displaystyle S_{i}} , remove all gaps. == Graphing approach == A general approach when calculating multiple sequence alignments is to use graphs to identify all of the different alignments. When finding alignments via graph, a complete alignment is created in a weighted graph that contains a set of vertices and a set of edges. Each of the graph edges has a weight based on a certain heuristic that helps to score each alignment or subset of the original graph. === Tracing alignments === When determining the best suited alignments for each MSA, a trace is usually generated. A trace is a set of realized, or corresponding and aligned, vertices that has a specific weight based on the edges that are selected between corresponding vertices. When choosing traces for a set of sequences it is necessary to choose a trace with a maximum weight to get the best alignment of the sequences. == Alignment methods == There are various alignment methods used within multiple sequence to maximize scores and correctness of alignments. Each is usually based on a certain heuristic with an insight into the evolutionary process. Most try to replicate evolution to get the most realistic alignment possible to best predict relations between sequences. === Dynamic programming === A direct method for producing an MSA uses the dynamic programming technique to identify the globally optimal alignment solution. For proteins, this method usually involves two sets of parameters: a gap penalty and a substitution matrix assigning scores or probabilities to the alignment of each possible pair of amino acids based on the similarity of the amino acids' chemical properties and the evolutionary probability of the mutation. For nucleotide sequences, a similar gap penalty is used, but a much simpler substitution matrix, wherein only identical matches and mismatches are considered, is typical. The scores in the substitution matrix may be either all positive or a mix of positive and negative in the case of a global alignment, but must be both positive and negative, in the case of a local alignment. For n individual sequences, the naive method requires constructing the n-dimensional equivalent of the matrix formed in standard pairwise sequence alignment. The search space thus increases exponentially with increasing n and is also strongly dependent on sequence length. Expressed with the big O notation commonly used to measure computational complexity, a naïve MSA takes O(LengthNseqs) time to produce. To find the global optimum for n sequences this way has been shown to be an NP-complete problem. In 1989, based on Carrillo-Lipman Algorithm, Altschul introduced a practical method that uses pairwise alignments to constrain the n-dimensional search space. In this approach pairwise dynamic programming alignments are performed on each pair of sequences in the query set, and only the space near the n-dimensional intersection of these alignments is searched for the n-way alignment. The MSA program optimizes the sum of all of the pairs of characters at each position in the alignment (the so-called sum of pair score) and has been implemented in a software program for constructing multiple sequence alignments. In 2019, Hosseininasab and van Hoeve showed that by using decision diagrams, MSA may be modeled in polynomial space complexity. === Progressive alignment construction === The most widely used approach to multiple sequence alignments uses a heuristic search known as progressive technique (also known as the hierarchical or tree method) developed by Da-Fei Feng and Doolittle in 1987. Progressive alignment builds up a final MSA by combining pairwise alignments beginning with the most similar pair and progressing to the most distantly related. All progressive alignment methods require two stages: a first stage in which the relationships between the sequences are represented as a phylogenetic tree, called a guide tree, and a second step in which the MSA is built by adding the sequences sequentially to the growing MSA according to the guide tree. The initial guide tree is determined by an efficient clustering method such as neighbor-joining or unweighted pair group method with arithmetic mean (UPGMA), and may use distances based on the number of identical two-letter sub-sequences (as in FASTA rather than a dynamic programming alignment). Progressive alignments are not guaranteed to be globally optimal. The primary problem is that when errors are made at any stage in growing the MSA, these errors are then propagated through to the final result. Performance is also particularly bad when all of the sequences in the set are rather distantly related. Most modern progressive methods modify their scoring function with a secondary weighting function that assigns scaling factors to individual members of the query set in a nonlinear fashion based on their phylogenetic distance from their nearest neighbors. This corrects for non-random selection of the sequences given to the alignment program. Progressive alignment methods are efficient enough to implement on a large scale for many (100s to 1000s) sequences. A popular progressive alignment method has been the Clustal family. ClustalW is used extensively for phylogenetic tree construction, in spite of the author's explicit warnings that unedited alignments should not be used in such studies and as input for protein structure prediction by homology modeling. European Bioinformatics Institute (EMBL-EBI) announced that CLustalW2 will expire in August 2015. They recommend Clustal Omega which performs based on seeded guide trees and HMM profile-profile techniques for protein alignments. An alternative tool for progressive DNA alignments is multiple alignment using fast Fourier transform (MAFFT). Another common progressive alignment method named T-Coffee is slower than Clustal and its derivatives but generally produces more accurate alignments for distantly related sequence sets. T-Coffee calculates pairwise alignments by combining the direct alignment of the pair with indirect alignments that aligns each sequence of the pair to a third sequence. It uses the output from Clustal as well as another local alignment program LALIGN, which finds multiple regions of local alignment between two sequences. The resulting alignment and phylogenetic tree are used as a guide to produce new and more accurate w

Automated dispensing cabinet

An automated dispensing cabinet (ADC), also called a unit-based cabinet (UBC), automated dispensing device (ADD), or automated dispensing machine (ADM)[1], is a computerized medicine cabinet for hospitals and healthcare settings. ADCs allow medications to be stored and dispensed near the point of care while controlling and tracking drug distribution. == Overview == Hospital pharmacies have provided medications for patients by filling patient-specific cassettes of unit-dose medications that were then delivered to the nursing unit and stored in medication cabinets or carts. ADCs, originally designed for hospital use, were introduced in hospitals in the 1980s and have facilitated the transition to alternative delivery models and more decentralized medication distribution systems.[2] Implementing automated dispensing cabinets as part of a decentralized or hybrid medication distribution system can improve patient safety and the accountability of the inventory, streamline certain billing processes. However, in the 2000s, the technology began to be deployed into other care settings where medication doses were stored onsite, and higher security methods were needed to control inventory, access, and dispensing of each patient dose. Settings that now deploy ADCs include long-term care facilities, hospice, critical access hospitals, surgery centers, group homes, residential care facilities, rehab and psych environments, animal health, dental clinics, and nursing education simulation. These diverse care settings share a common need to safely store, account for, and dispense individual doses of medications, especially narcotics and high-value medications, at the point of care.[3] ADCs track user access and dispensed medications, and their use can improve control over medication inventory. The real-time inventory reports generated by many cabinets can simplify the filling process and help the pharmacy track expired drugs. Furthermore, by restricting individual drugs – such as high-risk medications and controlled substances – to unique drawers within the cabinet, overall inventory management, patient safety, and medication security can be improved. Automated dispensing cabinets allow the pharmacy department to profile physician orders before they are dispensed.[4] ADCs can also enable providers to record medication charges upon dispensing, reducing the billing paperwork the pharmacy is responsible for. In addition, nurses can note returned medications using the cabinets' computers, enabling direct credits to patients' accounts. Since automated cabinets can be located on the nursing unit floor, nursing have speedier access to a patient's medications. Also, shorter waiting time ensures improved patient comfort and care.[5] == Role of automated dispensing in healthcare == Automated dispensing is a pharmacy practice in which a device dispenses medications and fills prescriptions. ADCs, which can handle many different medications, are available from a number of manufacturers such as BD, ARxIUM, and Omnicell. Though members of the pharmacy community have been utilizing automation technology since the 1980s, companies are constantly improving ADCs to meet changing needs and health standards in the industry. Several goals can be met by implementing an automated product in a healthcare facility. Patient safety can be ensured with the use of ADC technology such as barcoding. Anesthesia ADCs in operating rooms and perioperative areas may include label printing to prevent mix-ups such as errors between morphine and hydromorphone, two different opioid analgesics that frequently get confused. These systems also communicate with the pharmacy and its information management system to track medications removed and support inventory replenishment. == Key features == ADCs are like automated teller machines whose specific technologies such as barcode scanning and clinical decision support can improve medication safety. Some have metal locking drawers for added security and some have automated single-dose dispensing to prevent the need for a blind count each time a controlled substance is accessed. Over the years, ADCs have been adapted to facilitate compliance with emerging regulatory requirements such as pharmacy review of medication orders and safe practice recommendations. ADCs incorporate advanced software and electronic interfaces to synthesize high-risk steps in the medication use process. These unit-based medication repositories provide computer-controlled storage, dispensation, tracking, and documentation of medication distribution in the resident care unit. Since automated dispensing cabinets are not located in the pharmacy, they are considered "decentralized" medication distribution systems. Instead, they can be found at the point of care on the resident care unit. Tracking of the stocking and distribution process can occur by interfacing the unit with a central pharmacy computer. These cabinets can also be interfaced with other external databases such as resident profiles, the facility's admission/discharge/transfer system, and billing systems. Most ADC providers offer scalable systems since several important factors vary widely by facility such as budget, physical room size, patient population/demographics, type of healthcare facility, etc.

MyChild App

MyChild App is an Android app that helps parents screen developmental disorders in their children between the age of 1 and 24 months. The app contains information for parents about the different stages of a child's development. == Background == Launched in 2015 on Google PlayStore, the app is a consumer product of the parent company, Time Ahead, Inc. Its office is based in Bhopal, Madhya Pradesh, India. As of August 2016, the app had been downloaded by 11,000+ users in 140+ countries and is a part of fbstart case study. == Funding == In 2015, MyChild App raised a seed round of $100k led by 500 Startups, followed by angel investors Samir Bangara, Anisha Mittal, Pallav Nadhani, Deobrat Singh, Lalit Mangal, Arihant Patni, Amit Gupta, Dr. Ritesh Malik, Saurab Paruthi, and Singapore Angel Network.

Security switch

A security switch is a hardware device designed to protect computers, laptops, smartphones and similar devices from unauthorized access or operation, distinct from a virtual security switch which offers software protection. Security switches should be operated by an authorized user only; for this reason, it should be isolated from other devices, in order to prevent unauthorized access, and it should not be possible to bypass it, in order to prevent malicious manipulation. The primary purpose of a security switch is to provide protection against surveillance, eavesdropping, malware, spyware, and theft of digital devices. Unlike other protections or techniques, a security switch can provide protection even if security has already been breached, since it does not have any access from other components and is not accessible by software. It can additionally disconnect or block peripheral devices, and perform "man in the middle" operations. A security switch can be used for human presence detection since it can only be initiated by a human operator. It can also be used as a firewall. == Types == === Hardware kill switch === A hardware kill switch (HKS) is a physical switch that cuts the signal or power line to the device or disable the chip running them. == Examples == A cellphone is compromised by malicious software, and the device initiates video and audio recording. When the user activates the “prevent capture of audio/video” mode of the security switch, that either physically disconnects or cut the power to the microphone and the camera, which stops the recording. A laptop that has an embedded security switch is stolen. The security switch detects a lack of communication from a specific external source for 12 hours, and responds by disconnecting the screen, keyboard and other key components, rendering the laptop useless, with no possibility of recovery, even with a full format. A user wishes to prevent tracking of their location. The user then activates geolocation protection and the security switch disables all GPS communication, eliminating the possibility of tracking the device's location. A user desires to eliminate the possibility of their PIN being copied from their smartphone. They can activate the secure input function, causing the security switch to disconnect the touch screen from the operating system, so input signals are not available to any devices except the switch. A security switch performs scheduled monitoring and finds that a program is attempting to download malicious content from the internet. It then activates internet security function and disables internet access, interrupting the download. If laptop software is compromised by air-gap malware, the user may activate the security switch and disconnect the speaker and microphone, so it can not establish communication with the device. == History == Google started to work on a hardware kill switch for AI in 2016. In 2019, Apple, and Google, along with a handful of smaller players, are designing “kill switches” that cut the power to the microphones or cameras in their devices. Googles first product that implemented this is Nest Hub Max. Hardware kill switches are already available and widely tested on the PinePhone, Librem, Shiftphone, to cut power to the input peripherals (microphone, camera) but also the network connectivity modules (wifi, cellular network).

Groover

Groover is an online platform, record label and distributor, connecting artists and musicians with music professionals and media outlets. The service was founded in 2018 in France and operates from offices in Paris and New York. The platform has over 3,000 active contacts, including SPIN Magazine and Sofar Sounds. Groover uses a micro-payment model. Among the platform's over 500,000 regular users are record labels such as Ninja Tune, Ba Da Bing Records, Dance To The Radio, Roche Musique, Wagram Music, Secret City Records, and artists including Bonobo, Michael Bolton, Aloe Blacc, Haddaway, Passenger, La Femme and Chinese Man. == History == Groover was launched at the MaMA Music Convention in October 2018. It was co-founded by Dorian Perron, Romain Palmieri, and Rafaël Cohen while they were students at UC Berkeley. Initially growing in France, the company has expanded to the United States, Canada, the United Kingdom, Brazil, Italy, and elsewhere in Europe. In March 2019, Groover was part of the Business France delegation at the South by Southwest (SXSW) festival. In June 2019, Groover raised €1.3 million from various angel investors. In April 2021, Groover acquired the platform Soonvibes, which had 70,000 users at the time, in order to strengthen its community in the electronic music space. In November 2021, Groover announced a €6 million funding round from Bpifrance Creative Industries and Partech. Between 2023 and 2025, Groover entered strategic partnerships with major artist service providers, including CD Baby, TuneCore, SoundCloud, UnitedMasters, Symphonic Distribution, Audiomack and SACEM. In February 2024, Groover announced a Series A funding round of $8 million from OneRagTime, Trind, Techmind, and Mozza Angels. == Function == Using a micro-payment system, professionals listen to tracks and provide written feedback. These professionals retain full editorial independence and are under no obligation to share the track or contact the artist. == Awards == 2nd Prize for Music Innovation 2023 from the Centre national de la musique (France) "Future Creator" Award at the Petit Poucet Competition 2019 Jury's Special Mention at the MaMA Invent 2019 competition 1st Prize for Digital Initiative in Culture, Communication & Media 2019 awarded by Audiens "Start-up of the Year" at the Social Music Awards 2020 French American Entrepreneurship Award 2022 at the French Consulate in New York

Customer support

Customer support is a range of services to assist customers in making cost effective and correct use of a product. It includes assistance in planning, installation, training, troubleshooting, maintenance, upgrading, and disposal of a product. Regarding technology products such as mobile phones, televisions, computers, software products or other electronic or mechanical goods, it is termed technical support. It aims to ensure users can effectively operate the product and resolve any issues that may arise throughout its lifecycle. Support is delivered through various channels, including telephone, email, live chat, self-service knowledge bases, and social media. Research indicates that most customers attempt to resolve issues through self-service before contacting a representative. For products sold across multiple regions, support may be provided in several languages, as consumers tend to prefer assistance in their native language. Requirements for customer contact centres are defined in international standards such as ISO 18295.

System integrity

In telecommunications, the term system integrity has the following meanings: That condition of a system wherein its mandated operational and technical parameters are within the prescribed limits. The quality of an AIS when it performs its intended function in an unimpaired manner, free from deliberate or inadvertent unauthorized manipulation of the system. The state that exists when there is complete assurance that under all conditions an IT system is based on the logical correctness and reliability of the operating system, the logical completeness of the hardware and software that implement the protection mechanisms, and data integrity.