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Infographic – IBM Leads Again in Patent Awards

Chart: patents awarded in 2018

Click on image for full size view. (Statista)

17 Aug. 2019. One measure of a company’s culture for innovation is the number of patents granted for its inventions. Of course, other factors affect that number, such as the size of the business and number of intellectual property lawyers it can call upon. That may explain IBM’s leading all companies in the number of U.S. patents awarded in 2018, and for the 26th year in a row.

Our friends at Statista prepared a chart this week with data from an annual report by the Intellectual Property Owners Association, this weekend’s infographic on Science & Enterprise. The graphic shows IBM with more than 9,000 patents last year assigned to the company, the owners of the rights to the intellectual property.  Samsung’s inventors received more than 5,800 patents in 2018, followed by Canon with some 3,200 patents. The next nine spots, with 2,100 to 2,800 patents are major technology companies, particularly semiconductor and hardware manufacturers, but also Alphabet/Google, Microsoft, and Apple.

Patents are no guarantee of developing innovative products and services, but they offer an early sign of where those innovations may happen.

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Disclosure: The author owns shares in IBM.

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Skin Sensor Network Tracks Health Functions

Printed sensor

Sensor circuits screen-printed on clear thin plastic (Bao Lab, Stanford University)

16 Aug. 2019. An engineering team designed sensors that stick on the skin and form a network with radio-frequency signals to track physiological functions. Researchers from Stanford University in California and Nanyang Technological University in Singapore describe the sensor network in yesterday’s issue of the journal Nature Electronics (paid subscription required).

A team from the labs of Stanford chemical engineering professor Zhenan Bao and Nanyang materials scientist Chen Xiaodong are seeking more effective techniques for using wearable sensors to capture personalized health data from individuals. The wide use of smartphones provide provide a basic platform for hosting and capturing data from wearable devices, and the researchers aim to provide lightweight, inexpensive, and unobtrusive sensors to record a person’s health indicators. Their sensors need to be comfortable enough for a person to wear, with no rigid circuits nor batteries.

Their solution is a set of sensors on flexible and stretchable plastic that sticks directly to the skin. The sensor circuits are screen-printed on clear, thin plastic that flexes and stretches with the skin. The initial set of circuits reported in the journal paper are designed to measure movements, such as tightening of the skin, and pulse rate. The circuitry includes a radio-frequency antenna that beams the sensor data to a nearby receiver.

Transmitting the sensor data proved to be a particular challenge, say the researchers. The screen-printed antenna is designed to capture power from the nearby receiver, rather than carrying its own power source, one of the design specifications. The flexing and bending of the radio-frequency antenna, however, weakens and destabilizes signals from the sensors.

The team’s solution separated the signal-receiving device from the smartphone. The receiver is now clipped or sewn on clothing very close to the sensor, so it can pick-up even a weak signal. The battery-powered receiver then transfers the data via Bluetooth when pinged by the smartphone.

To prove the concept, the Stanford-Nanyang team asked a volunteer to wear motion sensors that measured breathing and body movement, as well as a pulse-rate sensor. Receivers were clipped on clothing worn over the sensors to capture the data, which were then relayed to mobile systems for analysis and display. The researchers report the sensors simultaneously captured and continuously relayed data from the test sensors for processing.

The team now aims to add sensors for more functions, such as perspiration and body temperature. But the system aims to offer a network of sensors the researchers call BodyNet that can be worn on the skin on various parts of the body, capturing data with receivers woven into clothing, and not necessarily positioned directly over the sensor.

“We think one day it will be possible to create a full-body skin-sensor array to collect physiological data without interfering with a person’s normal behavior,” says Bao in a university statement. The researchers filed a patent for the BodyNet technology.

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Hispanic Neuro Disease Landscape Mapped in New Study

Brittany Dugger

Brittany Dugger (University of California in Davis)

16 Aug. 2019. A new project examines brain pathologies leading to development of Alzheimer’s disease in Americans of Hispanic descent, a group largely ignored in neuroscience. The five-year effort by researchers at University of California in Davis and other institutions, is funded by a $3.8 million award from National Institute on Aging, part of National Institutes of Health.

A team led by pathology professor Brittany Dugger at the UC-Davis medical school is seeking to better define brain conditions and disorders in Hispanic-Americans, the fastest growing ethnic group in the U.S., to provide insights for detecting and treating disorders such as Alzheimer’s disease. The university cites data showing Americans of Hispanic descent are more likely to suffer diseases in the brain affecting blood vessels, such as stroke, and are at a higher risk of developing Alzheimer’s disease than non-Hispanic whites in the U.S.

Yet, relatively little is known about degenerative diseases in the brain among people in this ethnic group. “There is little information on the pathology of dementia affecting people from minority groups, especially for individuals of Mexican, Cuban, Puerto Rican, and Dominican descent,” says Dugger in a university statement. She notes that “this grant will allow us to build on our expertise in dementia research to gain better understanding of Alzheimer’s disease in these communities and provide insights to improve prevention and treatment.”

To fill this gap, Dugger and colleagues plan to assemble data on neurodegenerative diseases among American Hispanics. The data are expected to show the presence, location, and density of conditions related to Alzheimer’s disease, such as amyloid plaque and tau-protein build-ups on nerve cells, as well as indicators of stroke and other blood-vessel disorders in the brain.

The team plans to study donated postmortem samples of brain tissue from 100 people of Mexican, Cuban, Puerto Rican, and Dominican descent provided by Alzheimer’s disease research centers at UC-Davis, UC-San Diego, and Columbia University in New York. Data from these samples will then be compared to comparable brain tissue samples from 200 non-Hispanic white individuals.

Further analysis will investigate clinical, genetic, and demographic factors affecting Alzheimer’s disease and dementia. The findings are expected to highlight variables such as status of an individual’s apolipoprotein E or APOE gene where some variations are associated with Alzheimer’s disease, clinical history of stroke, hypertension, or diabetes, and demographic variables including sex and education.

Dugger adds, “[W]e will look at the co-presence of cerebrovascular disease and Alzheimer’s disease. For people who had strokes, we would like to know, where did these strokes happen? When did they happen? How big they were? Did the patient have other vessel pathologies? How healthy do these vessels look?”

The UC-Davis team plans to partner with Michael Keiser at UC-San Francisco to apply machine learning algorithms for preparing neuropathology profiles and pinpointing the underlying factors affecting development of Alzheimer’s disease and dementia in this population. The findings are expected to help devise better diagnostic, treatment, and prevention strategies, including precision medicine for brain disorders among Hispanic Americans.

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Controlled Brain Tumor Gene Therapy Shown Safe

Brain tumor graphic

(National Science Foundation)

15 Aug. 2019. A clinical trial shows an experimental gene therapy that controls release of a powerful anti-tumor protein is safe for patients with stubborn glioblastoma, a type of brain cancer. Results of the trial testing the treatment, made by the company Ziopharm Oncology Inc. in Boston, appear in yesterday’s issue of the journal Science Translational Medicine (paid subscription required).

Researchers led by neurosurgery professor Antonio Chiocca at Brigham and Women’s Hospital in Boston, are seeking better therapies for glioblastoma, an aggressive brain cancer that affects astrocyte or glial cells supporting neurons or nerve cells in the brain. Glioblastoma is often difficult to treat, where usually the best hope is to slow progression of the disease with radiation or chemotherapy. Survival from initial tumors is typically 15 months and those with recurring glioblastoma usually survive for less than a year.

Chiocca and colleagues, from several cancer centers in the U.S. and Ziopharm Oncology, tested the company’s gene therapy for glioblastoma that transfers genes coding for the immune-system protein interleukin-12 into the region of the brain after removing the tumor. The gene is injected into the brain cavity and delivered with an adenovirus, a type of virus benign to most people.

Interleukin-12 is a powerful protein that activates T-cells in the immune system to attack tumors, but those same properties can lead to dangerous adverse effects for cancer patients. Before surgery, patients are given the drug capsule veledimex that activates interleukin-12 to produce tumor-attacking T-cells, with the amount of interleukin-12 released dependent on the patient’s dosage of veledimex. Patients then continue taking veledimex for 14 days following the surgery.

The early-stage clinical trial is recruiting 48 participants with recurring glioblastoma at several cancer centers in the U.S., and looking primarily for signs of adverse effects of the treatments, with doses of veledimex ranging from 20 to 120 milligrams per day. The journal paper reports on 31 participants in the trial, with results showing adverse effects including cytokine release syndrome, which often occurs with immunotherapies, most likely to occur at higher doses of veledimex. The researchers say the adverse effects were reversed by discontinuing the treatments.

The team also tracked activity of drugs in the body, and found higher doses of veledimex resulted in higher concentrations veledimex, as well as interleukin-12, or IL-12, and interferon-gamma, a by-product protein in the immune system, in the patients blood. And while the number of participants was too small to draw conclusions, patients in the trial taking 20 milligrams of veledimex reported a median overall survival time of 12.7 months.

Some participants also took corticosteroids to control inflammation in the brain, but corticosteroids also have a dampening effect on immunotherapies. Patients taking minimal corticosteroids and 20 milligrams of veledimex reported median overall survival times of 17.8 months. The researchers say these survival rates are longer than historical averages for recurring glioblastoma patients.

“We believe these study results show it is now possible to have regulatable immunotherapy via genes,” says Chiocca in a Ziopharm Oncology statement. “Controlled IL-12 is well-tolerated in patients with glioblastoma, with encouraging evidence that the drug is having its intended effect.” Chiocca tells more about the clinical trial and treatment in this video hosted on the EurekAlert web site.

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Nanotube Fibers Configured for Heart Repair

Inspecting a fiber

Matteo Pasquali, left, and Mehdi Razavi inspect a spool of carbon nanotube fiber. (Texas Heart Institute)

14 Aug. 2019. Medical and engineering researchers developed fibers made with nanoscale carbon tubes that in lab animals conducted electrical signals and repaired heart damage. A team from Texas Heart Institute and Rice University in Houston describe their findings with the fibers in the 12 August issue of the journal Circulation: Arrhythmia and Electrophysiology.

The biocompatible fibers are a result of work by electro-physiologist Mehdi Razavi at Texas Heart Institute and engineering professor Matteo Pasquali at Rice University. The researchers are seeking better treatment methods for ventricular tachycardia, arrhythmias or irregular heart rhythms caused by abnormal electrical signals from the ventricles, the lower chambers of the heart. Current treatments use implanted defibrillators, drugs, or ablation that can improve heart pacing, but do not address the slowing heart beat velocity. And more recent advances with stem cells and gene therapy are still in very early stages.

The team’s solution is fibers made of nanoscale carbon tubes with a protective polymer coating, developed in Pasquali’s lab, used like sutures to repair damaged heart tissue. The carbon nanotubes carry electrical signals, with the polymer coating stripped off the ends allowing them to act like electrodes.

“These arrhythmias are caused by the disorganized firing of impulses from the heart’s lower chambers,” says Razavi in a joint statement, “and are challenging to treat in patients after a heart attack or with scarred heart tissue due to such other conditions as congestive heart failure or dilated cardiomyopathy.” Pasquali adds that the flexibility of the fibers make them good candidates for this task. “Flexibility is important because the heart is continuously pulsating and moving, so anything that’s attached to the heart’s surface is going to be deformed and flexed.”

The researchers tested the fibers in sheep, whose hearts are similar in size and function to humans, induced with abnormal heart rhythms. The results show that sheep with the carbon nanotube sutures improved their heart rhythms, compared to similar sheep using silk sutures, and maintained normal rhythms for a month.

The team also tested the carbon nanotube fibers on mice and rats induced with both acute heart damage, such as a heart attack, and chronic heart disorders. The results show the carbon nanotube sutures restored normal heart pacing in rodents with both acute and chronic heart conditions, although animals with chronic heart disorders also required pacemakers. Postmortem tests with the mice and rats show no evidence of toxicity from the fibers.

While the animal tests are encouraging, the authors note that techniques are needed, such as insertion or implantation by minimally-invasive catheters, are still needed before carbon nanotube fibers can be tested in humans. Several authors filed for a patent on the carbon nanotube technology, and started the company NanoLinea Inc. in Houston to take it to market. Colin Young, a co-author of the paper is NanoLinea’s CEO.

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Neuro Stimulation Reduces Stroke Muscle Weakness

Neurons

(commonfund.nih.gov)

13 Aug. 2019. A clinical trial shows a non-invasive device stimulating the spinal cord and upper limb muscles reduces spasticity and muscle weakness in people who suffered a stroke. Results from the trial appear in the 23 July issue of the journal Bioelectric Medicine.

The trial is testing the Myoregulator system made by PathMaker Neurosystems Inc. in Boston and Paris for reducing muscle spasticity and muscle weakness in people who experience a stroke. In neuromotor spasticity muscles are continuously contracted, which interferes with normal speech and movements. The condition, marked by muscle tightness and involuntary movements, is a symptom of stroke, but also other neuromuscular disorders including cerebral palsy, multiple sclerosis, and spinal cord injury.

The Myoregulator system simultaneously stimulates nerve pathways in the spinal cord and peripheral nerves in the affected limbs. Electrodes are placed on the skin on two sides of the spinal cord — usually back and abdomen — sending an electric current through the spinal cord, a process called trans-spinal direct current stimulation. At the same time, the Myoregulator attaches electrodes on the skin over muscles in the arms and wrist experiencing spasticity and muscle weakness, a technique called peripheral nerve direct current stimulation. Nerve stimulation sessions last for about 20 minutes.

The clinical trial enrolled 26 individuals at the Feinstein Institute for Medical Research in Manhasset, New York who suffered a stroke and are experiencing hand and wrist spasticity. Participants received 20-minute nerve stimulation sessions once a day for 5 consecutive days, first with a sham device, then with a working MyoRegulator system, separated by a one week wash-out period. Participants — who were not told which were the sham and real sessions — were rated on days 3 and 5, on measures of muscle resistance and a standard scale of spasticity, after both the sham and real nerve stimulation sessions, then after 5 weeks.

The results show the 20 participants completing the program experienced less muscle resistance and spasticity at the end of the MyoRegulator sessions compared to the sham stimulation. And the reduced muscle resistance and spasticity measures persisted for 5 weeks following the last real stimulation treatment.

The research team also rated participants on standard scales of motor functions after a stroke, Fugl-Meyer Assessment and Wolf Motor Function Test. Individuals in the trial completing the full stimulation program and follow-up evaluations, 16 of the original 26 participants, were rated on these measures. The results show by the follow-up evaluations, participants improved their upper-limb motor functions in addition to reducing spasticity and weakness. Stroke patients, say the researchers, usually require specialized rehabilitation training to achieve these results.

Bruce Volpe, a professor in the Feinstein Institute’s molecular medicine department and principle investigator on the project, says in an institute statement, “The surprise in these clinical results were the improved motor functions that apparently occurred with the focused treatment only of spasticity. We are eager to start a trial that couples motor training and anti-spasticity treatment.”

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Trial Shows Two Drugs Can Treat Ebola Virus

Ebola virus

Ebola virus (Defense.gov)

13 Aug. 2019. A clinical trial in the Congo shows two different therapies made with synthetic antibodies are better able to treat Ebola infections than two other drugs tested. National Institute of Allergy and Infectious Diseases, or NIAID, also said yesterday results of the trial were conclusive enough to stop the full trial early and recommended extending the study with only the two more effective treatments: REGN-EB3 made by Regeneron Pharmaceuticals and mAb114 from Ridgeback Biotherapeutics.

The most recent Ebola outbreak is taking place in Democratic Republic of the Congo in central Africa that began in the summer of 2018. World Health Organization says as of 28 July, 2,577 cases of Ebola are confirmed in the country, causing 1,696 deaths. Adding in probable occurrences of Ebola, the numbers increase to 2,671 total cases and 1,790 deaths.

The mid- and late-stage clinical trial, known as the PALM study — short for Pamoja Tulinde Maisha, a Swahili phrase that roughly translates to Together Save Lives — is enrolling 1,050 participants, both children and adults, at four sites in the Congo diagnosed with early Ebola virus infections. Participants are randomly assigned to receive one of four Ebola therapies, one current drug and three experimental treatments:

ZMapp by Mapp Biopharmaceutical, already approved as an Ebola treatment and considered the standard of care

REGN-EB3 by Regeneron Pharmaceuticals

mAb114 by Ridgeback Biotherapeutics

Remdesivir by Gilead Sciences

The PALM trial began in November 2018, and as of 9 August enrolled 681 participants. The research team from NIAID, Congolese health authorities, and international medical humanitarian groups is looking primarily at relative mortality rates of participants after 28 days, as well as presence of Ebola virus in participant blood samples and serious adverse effects at various points up to 28 days.

Preliminary results with 499 participants show individuals with Ebola receiving REGN-EB3 and mAb114 have a greater chance of survival than those receiving ZMapp or remdesivir. The trial’s independent data and safety monitoring board recommended the full trial be stopped, but the study continue with participants randomly assigned to receive either REGN-EB3 or mAb114. The preliminary data, says the board, are compelling enough to recommend and implement this change in procedure.

“REGN-EB3 is a three-antibody cocktail designed with the goal of enhancing efficacy, reducing the development of viral sequences that lead to resistance, and increasing potential utility in future outbreaks as viruses continually evolve,” says Christos Kyratsous, vice president of research, infectious diseases and viral vector technologies at Regeneron in a company statement.

As reported by Science & Enterprise, Regeneron, in Tarrytown, New York, received a contract in September 2015 from Biomedical Advanced Research and Development Authority, or BARDA to develop a synthetic highly-target human antibody to treat Ebola. BARDA is an agency of the U.S. Department of Health and Human Services.

mAb114 is also a synthetic antibody, originally developed by NIAID — part of National Institutes of Health — and labs in the Democratic Republic of the Congo and Switzerland, as an Ebola treatment. The antibody is based on samples taken from survivors of a 1995 Ebola outbreak in the Congo, Ridgeback Biotherapeutics, a biotechnology company in Miami, Florida, licensed mAB114 from NIAID in December 2018 for further development.

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Engineered Bacteria Hydrogels Designed for Gut Repair

Nanofibers from engineered E. coli

Nanofiber network produced by genetically engineered E. coli bacteria (Wyss Institute, Harvard University)

12 Aug. 2019. Biomedical engineers genetically altered bacteria that when added to gel materials can be applied like a spray or ointment to help heal intestinal surfaces. Researchers from labs at Harvard University and its affiliated Brigham and Women’s Hospital in Boston describe their discoveries in today’s issue of the journal Advanced Materials (paid subscription required).

A team from the Harvard lab of Neel Joshi that studies biologically fabricated materials, part of the Wyss Institute for Biologically Inspired Engineering, is seeking better techniques for healing wounds in the gut. Layers of mucous line the insides of the human gut that resist normal adhesives, making it difficult for even surgically-applied materials to stick to internal wounds. In addition, the complex nature of the human gut requires a solution that can be adjusted to work with surfaces other than mucous membranes, having different properties.

Joshi’s lab studies properties of bacteria, including the millions of strains living in the gut that can be adapted to produce living materials with therapeutic characteristics, rather than pathogens. One of those materials is the lab’s biofilm-integrated nanofiber display, or Bind, that genetically engineers E. coil bacteria to produce biofilms with nanoscale fibers having desired properties. E. coli and biofilms are usually associated with food poisoning and antibiotic-resistant bacteria, but when genetically altered, they can perform helpful functions rather than have harmful effects.

In this case, Joshi and colleagues genetically engineered E. coli to express nanoscale fibers called curli, part of the cell framework produced by some bacteria to form biofilms, particularly for adhering to other cell surfaces. The bacteria were also engineered to bind to human trefoil factors, peptides secreted by mucous cells to protect the intestinal surface tissue layer. The researchers added these curli- and trefoil factor-engineered bacteria to hydrogels, water-based and biocompatible polymer gels that can be administered with syringes or endoscopes into the gut.

In tests with samples of gut tissue from goats, the researchers found hydrogels with the altered E. coli expressing trefoil factors adhered to the mucous-lined surfaces in that tissue. In further tests with goat colon tissue, the team engineered E. coli to express fibronectin proteins found on serous membranes, a protective layer in the gut and other organs. In these tests, the hydrogels adhered to the serous layer, but not mucous-lined tissue.

In tests with lab mice, hydrogels with live cells — the researchers call them Live Gels — could be taken orally, survive the harsh stomach environment, and reach the entry to large intestine with the engineered live bacteria intact. Also, bacteria designed for a particular type of trefoil factor or TFF, were retained in the mice colons. “The presence of bacteria in Live Gels prolonged their residency times in the gut from one day to at least five days,” says Joshi in a Wyss Institute statement, “due to the bacteria’s ability to continuously regenerate the curli fiber networks that are decorated with TFFs, without affecting the health of mice in any obvious way.”

Co-author Jeffrey Karp, a biomedical engineering professor at Brigham and Women’s Hospital adds, “Since hydrogels with different TFF domains can be easily sprayed onto tissue surfaces with controllable adhesion and functional activity, we envision their potential use in endoscopic procedures to treat intestinal disorders, like a a spray-on bandage.”

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MD Anderson, Drug Maker Partner on Lung, GI Cancers

Cancer magnified

(PDPics, Pixabay)

12 Aug. 2019. MD Anderson Cancer Center and drug maker Boehringer Ingelheim agreed to jointly develop new treatments for lung and gastrointestinal cancers. Financial aspects of the multi-year collaboration were not disclosed.

The agreement calls for MD Anderson in Houston, part of the University of Texas system, to establish a “virtual research and development center” with Boehringer Ingelheim, based in Ingelheim, Germany. Under this arrangement, teams are expected to share data and analysis to advance Boehringer Ingelheim’s therapies for lung and gastrointestinal cancers. The cancer center and company cite data showing more than 4.1 million people die each year from lung and gastrointestinal cancers that include cancer of the throat, stomach, liver, pancreas, colon, and rectum. Lung cancers alone were responsible for 1.7 deaths in 2018.

The collaboration will focus initially on Boehringer Ingelheim’s research on inhibitors of KRAS gene pathways. The KRAS gene codes for proteins causing cells to proliferate, mature, and die. When it mutates, KRAS pathways are associated with some types of non-small cell lung cancer, colorectal cancer, and pancreatic cancer. The partnership is also investigating a receptor for human antibodies with the acronym TRAILR2, short for tumor necrosis factor-related apoptosis-inducing ligand, receptor 2. These antibodies shows promise in encouraging tumor cell death.

Taking part in the collaboration, is MD Anderson’s Traction unit, short for Translational Research to AdvanCe Therapeutics and Innovation in ONcology. This operation, says the cancer center, consists of clinicians, researchers, and drug development experts working on small molecule, biologic, and cell-based therapies. The platform is designed to advance promising cancer treatments through preclinical stages to meet standards for beginning early-stage clinical trials.

MD Anderson and Boehringer Ingelheim say the arrangement offers the flexibility to advance joint projects at various stages of development from initial research to clinical trials, over their collaboration time. “Together, we hope to transform the treatment landscape for these diseases by tackling their root causes and drivers, that have so far remained elusive, exploring new and smart ways of killing cancer cells,” says Victoria Zazulina,, Boehringer Ingelheim’s corporate vice president for oncology in a joint statement.

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Infographic – A.I. Venture Deals Reach New Highs

AI funding chart

Click on image for full-size view (Statista)

10 Aug. 2019. The total amount of venture capital worldwide raised by artificial intelligence start-up companies set a record in the second quarter of 2019, reaching $7.4 billion. And in that April – June 2019 period, venture investors closed 488 deals, the second largest number of A.I.-related deals in any quarter.

Data for this weekend’s infographic on Science & Enterprise come from our friends at CB Insights and Statista that put together the chart. The CB Insights report shows for the first time investments in U.S. A.I. start-ups made up less than half of the deals closed in the quarter. Investments in European and Chinese companies comprised the majority of the deals.

However, American start-ups raised the largest A.I.-related venture amounts in the second quarter, making up eight of the top 10 deals. Total amounts invested in A.I. start-ups each quarter have been steadily rising since 2015, according to the report. In 2018, the second quarter was also a big investment period for A.I., with start-ups worldwide raising some $7 billion.

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