In their 2014 Journal of the American Chemical Society paper, Li, Liskey, and Hartwig report on a nickel-catalyzed method for the borylation of aryl halides using diboron reagents. This process enables efficient and selective C–B bond formation in a range of aryl halides.

In their 2019 Journal of the American Chemical Society paper, Karmel, Chen, and Hartwig introduce a method for the palladium-catalyzed hydroamination of alkenes using ammonia, which provides a direct route for creating primary alkylamines.

In their 2015 Journal of the American Chemical Society paper, Cheng and Hartwig present a selective iridium-catalyzed method for the intramolecular borylation of aliphatic C–H bonds. This technique enables precise C–B bond formation on unactivated aliphatic carbon centers, achieving high selectivity without pre-functionalized substrates.

In their 2020 Journal of the American Chemical Society paper, Jones, Fast, and Schley report on a novel cobalt-catalyzed method for C–H activation and hydroarylation of alkenes. This reaction provides an efficient route for forming C–C bonds, enabling the hydroarylation of alkenes with high selectivity and under mild conditions.

In their 2012 Journal of the American Chemical Society paper, Ohmura, Torigoe, and Suginome describe a selective, nickel-catalyzed borylation of C(sp^3)–H bonds in aliphatic amines. This approach allows direct borylation of primary and secondary C–H bonds adjacent to nitrogen, creating versatile organoboron intermediates with high selectivity.

In their 2014 Chem. Communications paper, Ohmura, Torigoe, and Suginome introduce a novel method for site-selective borylation of aromatic compounds using a copper catalyst. This approach achieves high regioselectivity for C–H borylation, enabling selective functionalization of specific positions on aromatic rings, particularly useful in synthesizing complex organic molecules.

In this 2006 study, Murphy, Lawrence, Kawamura, Incarvito, and Hartwig report the development of a highly efficient and selective method for hydroamination of olefins using a platinum catalyst. The platinum complex effectively catalyzed C–N bond formation across a range of substrates under mild conditions.

In the 2000 paper by H. Chen, S. Schlecht, T. C. Semple, and J. F. Hartwig, published in Science, the authors present a pioneering study on the use of palladium catalysts for the direct amination of aryl halides. This work was groundbreaking as it demonstrated a highly efficient method for forming C–N bonds directly from aryl halides and amines.

J. F. Hartwig's 2016 paper covers key developments in transition metal-catalyzed processes that facilitate the direct functionalization of C–H bonds, often viewed as inert and difficult to modify selectively. Hartwig explores various catalytic systems, including palladium, iridium, and ruthenium catalysts, which have enabled efficient C–H activation under mild conditions, allowing for more sustainable approaches in synthesis by minimizing reliance on pre-functionalized starting materials.

Larsen and Dimmick described a correlation between biofilm growth and the surface area-to-volume ratio. This is based on the fact that, as the volume of an object decreases, the proportion of the surface area compared to the volume increases. In microchemostats with very low working volumes, this means there will be a higher proportion of surface-adhering bacteria compared to free-floating bacteria, facilitating biofilm formation.

Elowitz et al. and Atkinson et al. developed similar genetic circuits, aiming to induce oscillatory behavior in gene expression (which is based on protein production within a cell). In contrast, this study demonstrates intercellular, oscillatory behavior in cell growth and population dynamics.

You et al. demonstrated the functionality of a genetic circuit to regulate communication and population in E. Coli on a macroscopic scale. They expected the circuit to perform similarly when scaled down the microscopic level. Balagadde et al. used this circuit as a benchmark for their microchemostat by demonstrating consistent and stable oscillations in E. Coli populations over extended periods.

Starting with Kim and Lee (reference 8), researches are pushing towards smaller, more compact bioreactors for the benefits of miniaturization, which include using less resources, reduced costs, and benefiting from physics at the micro/nano scale.

Previous studies within living organisms have shown that other materials such as polyoctandiol citrate (POC), magnesium, silicon dioxide, and cellulose acetate may be good candidates for usage in bioresorbable devices and present biocompatible characteristics.

A previous study showed that nerve cooling is (i) not addictive - unlike opioid medication - (ii) does not permanently harm or disable affected nervous tissue, (iii) can be applied to a small targeted area without affecting surrounding tissue, (iv) does not produce an adverse response immediately after being applied, and (v) allows for the nerves being cooled to be simultaneously monitored to measure electrical activity so that the cooling can be adjusted if needed.

In the observations of Costerton et al., they have found the surface adhering bacteria making up biofilms differ physically to their free-floating counterparts.

The nervous system senses pain by transmitting messages from the site of injury to the brain, which interprets the signals as pain and prompts appropriate responses to protect the body. Scientists have found that they can control these signals using different methods like electricity, drugs, light, physical force, or changes in temperature. By using these methods, they can temporarily stop or block the messages in a specific area of the body, and they can do it in a way that the blocking can be reversed when needed. This approach allows researchers to manage pain or control certain body functions without causing permanent damage to the nerves.

Previous studies have shown that POC has a high elastic modulus, meaning that it can experience high stress and not become deformed. Furthermore, the rate at which it breaks down at the surface can be controlled, and it replicates the structure and mechanical properties of nervous tissue. The device developed by the authors in this paper needs all of these factors to function properly, making POC an ideal candidate.

Earlier studies have utilized bioresorbability to address similar problems associated with the removal of implantable sensors. The sensors can be designed to begin dissolving immediately after implantation, but remain functional for some time until the main components disintegrate. The duration of the dissolution process can be controlled by the type and thickness of materials within the device.

In a prior investigation, researchers simultaneously cooled two sciatic nerves, which extend from the hip to just below the knee, using different methods: one continuously and the other intermittently, for the same duration. They observed a significant discrepancy in response between the two nerves; specifically that though some tissue damage was caused by both intermittent and continuous cooling, the intermittent cooling caused much more severe tissue damage. This suggests that the response of sensory nerves to cooling is highly dependent on the cooling procedure and duration of exposure.

Peripheral nerves are the nerves outside of the brain and the spinal cord, extending through the rest of the body such as the arms and legs, and are responsible for sending and receiving information to and from the brain.

Cooling specific areas of the peripheral nervous system can cause a decrease in the speed of electrical impulses through the nerves and the strength of those impulses, making it more difficult for pain signals to reach the brain. Therefore, if the author can achieve contained, consistent cooling of certain nerves, they can prevent/reduce pain in patients.

This paper builds on research indicating that when the nerve environment cools down, the activity generating and transmitting nerve impulses decreases, thereby inhibiting the transmission of pain signals to the brain.

In past research, scientists have used peripheral nerve stimulation (PNS). This involves applying an electric field to certain areas of the spinal cord that send sensory signals to the brain. The electrical stimulation disrupts the nerves responsible for transmitting pain-related sensory information.

Previous studies have shown that electrical impulses in the nervous system can be blocked by lowering the temperature to 15°C or less, however, if the area is briefly heated, then this cooling threshold can be increased to around 21°C, or room temperature.

Zanzotto et al had developed a microscopic bioreactor for carrying out bacterial fermentation. Their device had sensors measuring 2 mm in diameter and can hold a volume as low as 5 µL, compared to the 500 mL of a typical bioreactor.

Here, the authors further miniaturized their bioreactor volume down to the nanoliter range/scale. For reference, 1 microliter is one millionth of a liter, while 1 nanoliter is one billionth of a liter.

Research from as early as the 1950s has found that different properties of bacteria can be studied by creating a stable environment with a constant source of nutrients. This has been backed up with mathematical models and led to the creation of the chemostat.

Lnp1 is a protein to maintain the structure of ER by stabilizing rearrangements of the ER networks.

Further reading: https://doi.org/10.1073/pnas.1805032115

Protein recycling and self-eating process that selectively happens in endoplasmic reticulum terms as ER-phagy (phagy means eating). Selective autophagy requires a receptor protein to recognize its degradation targets and directs the targets to be sequestrated by autophagosomes, a double membrane vesicle structure, which to be transported into lysosomes or vacuoles.

A protein named as Atg40, has been recognized as a ER-phagy receptor protein in yeast. FAM134B is a putative mammals homologue of ATG40.

Literature first explain the Atg40 ER-phagy receptor https://doi.org/10.1038/nature14506 (ATG40)

https://doi.org/10.1038/nature14498 (FAM134B)

Lst1-Sec23 is a coat adaptor protein that carry the cargo molecules form ER to Golgi, which mainly to help the secretory proteins transportation. The author discovered new function of the Lst1/Sec23 in self-eating and protein recycling process (autophagy), in which the Lst1-Sec23 functions together with the autophagy receptor, Atg40, to localize the ER domains for autophagic degradation.

In this paper, Pampaloni et. al discuss how the standard growth of cells on 2 dimensional surfaces does not accurately model organ-level functions such as nutrient/waste transportation. Contemporary research has worked on making 3D cell cultures made of cells and connective tissue, but no one has integrated multiple cell types with connective tissue in an "organ on a chip." In the end, the authors discuss the potential for microdevice technology to address the need for physiologically-relevant organ models in drug screening experiments.

When a human gets a lung infection, neutrophils are quick to respond to the infected site and ICAM-1 is over-expressed. These previous sources all characterize this aspect of the immune response of a lung infection. The migration of neutrophils and the expression of ICAM-1 inspired the authors as they tested the efficacy of the lung-on-a-chip. For example, the authors use TNF-a to trigger an immune response and measure the expression of ICAM-1 and presence of neutrophils at the exposure site

Pampaloni et. al. discuss the impact that extracellular matrix (ECM) has on cellular growth and development. The three-dimensional distribution of cells in an organ affects how cells--and even other organs--communicate with each other. In this way, "form fits function:" the physical characteristics of a set of tissues can dictate how nutrients and other biomolecules transport between cells. Drug screening is primarily performed on 2D cell cultures, where the functions of human tissues are not accurately represented. This work aims to directly address this issue

Takayama et. al report a new way of manufacturing microchannels out of PDMS that can be smaller than the width of a human hair! The process involves the controlled washing of a PDMS slab with chemicals. The authors have high hopes for their technology: "We believe that these procedures will enable new types of studies in fundamental cell biology, and that they will also be useful in the microfabrication of devices that require a high-level of control over the behavior of cells"

The following research papers discuss the potential for microfluidic devices to assess the problems with modern 3D tissue models. For example, Langer et al. discuss how standard cell cultures cannot replicate the repetitive mechanical strain that human organs such as lungs and gut undergo every day. The authors also discuss how oxygen and protein transport through these tissue scaffolds does not accurately mimic human conditions. While attempts have been made to improve cell-cell connectivity and nutrient transport in 3D cultures, microfluidic technology provides a potential pathway to generate accurate and viable organ models.

Montagu et al. reveal that the position of soil compaction affects root growth. When roots grow through compacted soil into uncompacted soil, total root growth is reduced. However, when roots grow through uncompacted soil into compacted soil, more compensatory root growth happens in the uncompacted soil and total root growth is not changed. This suggests that roots can sense soil compaction and avoid growing in compacted soil.

An and colleagues revealed that loss of EIL1 suppresses response to ethylene in Arabidopsis.

Alonso and colleagues characterized an ein2 mutant in Arabidopsis and found that ein2 mutant did not respond to ethylene.

Ma and colleagues identified a rice mutant that cannot respond to ethylene. They found that the mutation happened in a gene encodes a protein that is homologous to the EIN2 protein in Arabidopsis.

This work uses pPCO1:GFP-GUS and pPCO2:GFP-GUS as reporters of hypoxia condition.

An and colleagues reveal that the protein levels of EIN3 increase in response to ethylene. This is the fundment of using EIN3-GFP to measure ethylene response in plants.

Hussain and colleagues find that tomato plants with higher ethylene production have reduced growth in compacted soil when compared to tomato plants with lower ethylene production. This provides a connection between ethylene levels and plant growth in compacted soil.

This work reveals that air-filled porosity, bulk density, soil disturbance, the type of diffusion gases, and soil texture are factors that affects gas diffusion in soil.

A big goal in biomedical science is to make artificial organs that can be used to save lives. However, generating these new organs as well as integrating them into a human body has remained challenging. The cited articles discuss how hard it is to make organs that accurately mimic their human counterparts. If scientists could fabricate functional tissues and organs with integrated blood vessels to sustain them, artificial organ transplants could become a major therapeutic tool!

Davilla et. al. discuss the advantages and disadvantages of lab-grown cell cultures that can mimic the function of kidneys and livers. While these cultures are inexpensive and can help measure drug-specific tissue interactions at a cellular/molecular level, the models do not accurately account for molecular transport and toxicity interactions between tissues and organs. This is because the cultures are grown on a flat surface, rather than in a 3D organ-like configuration. The authors conclude that cell culture models are a step towards pharmaceutical testing that does not use animal models, but further development is needed to effectively mimic the human body's reactions to various drugs.

In this review article by famous tissue engineer Donald Ingber, there is great discussion of all the factors that affect cellular growth and development. In particular, the mechanical forces of tension and compression (as we see in the lungs when we inhale and exhale) can play a very important role in how cells divide, grow, and communicate. 3D cell cultures and lung-on-a-chip technology offer the potential to mimic these mechanical forces that we observe in the body. This accounting for human-like biology in drug testing has the potential to make animal studies obsolete!

Lst1-Sec23 is a coat adaptor protein that carry the cargo molecules form ER to Golgi, which mainly to help the secretory proteins transportation.

Protein recycling and self-eating process that selectively happens in endoplasmic reticulum terms as ER-phagy (phagy means eating). Selective autophagy requires a receptor protein to recognize its degradation targets and directs the targets to be sequestrated by autophagosomes, a double membrane vesicle structure, which to be transported into lysosomes or vacuoles.

A protein named as Atg40, has been recognized as a ER-phagy receptor protein in yeast. FAM134B is a putative mammals homologue of ATG40.

Literature first explain the Atg40 ER-phagy receptor https://doi.org/10.1038/nature14506 (ATG40)

https://doi.org/10.1038/nature14498 (FAM134B)

Lst1-Sec23 is a coat adaptor protein that carry the cargo molecules form ER to Golgi, which mainly to help the secretory proteins transportation. The author discovered new function of the Lst1/Sec23 in self-eating and protein recycling process (autophagy), in which the Lst1-Sec23 functions together with the autophagy receptor, Atg40, to localize the ER domains for autophagic degradation.

First ER-phagy receptors that were identified in yeast is ATG40, and FAM134B in mammals.

Lnp1 is a protein to maintain the structure of ER by stabilizing rearrangements of the ER networks.

Further reading: https://doi.org/10.1073/pnas.1805032115

Scientists have clearly shown that apoptosis takes place in different cell types and beginning at specific points/positions, it spreads through apoptotic cells at a constant speed.

This paper was able to demonstrate that the spreading of apoptosis through cells occurs via trigger waves.

Scientists have shown that the Xenopus egg extract is an effective medium for studying the process of apoptosis.

LMP results in the escape of protein-degrading proteins from the lysosomes to the cytoplasm, leading to initiation of cell death

RECS1 has features (di-aspartyl sensor and an arginine latch) found in related proteins in bacteria and humans, which are well investigated.

Here, RECS1 was reported to be an inhibitor (negative regulator) of apoptosis.

All these proteins negatively regulate programmed cell death

The functions of proteins in BCL-2 and the TMBIM family are similar across multiple organisms.

The sequence and structure of the mammalian RECS1 is closely related to the bacteria BsYetJ

Some authors, like Sherwood Idso, argued that scientists were vastly overestimating global warming. These claims were based on simplified atmospheric models, which neglect important features of Earth's energy balance. In 2016, global warming was measured to be 1.00°C above the 20th century average, consistent with the conventional models.

An earlier study presented a unified and systematic account of kinematics for mixing, blending, or stirring fluids. This work suggests that fluid mixing is the methodical stretching and folding of material lines and surfaces.

Jones et al. proposed a method of controlling the spread of materials along the direction of flow as they are transported in a cylindrical pipe (Poiseuille flow).

The authors made a multilayered electric dermis to provide tactile information to an amputee. The prosthesis and amputee demonstrate the ability to differentiate non-painful or painful stimuli using sensory feedback and a pain reflex feedback control system.

This group of researchers developed a skin-inspired mechanoreceptor, with output frequencies ranging between 0 and 200 hertz, which are pulses that mimic slow-adapting skin mechanoreceptors.

Shin et al, Lee et al, and Ma et al. have chosen to harness environmental humidity as the energy source for their robots. However, these robots have a limited speed of 6mm/s.

Rafsanjani et al. utilized Japanese paper folding techniques to create a soft robot mimicking the crawling motion of a snake. Similarly, Wang et al. employed inchworm movement patterns in their soft robots.

Many health and biotechnology research and assays depend on the efficient sorting of cells. Microfluidics allows for efficient and accurate cell sorting due to the ability to interact with cells using physical structures and processes occurring on the same scale. This is useful in drug development, disease detection, and cellular research.

Chaotic flow allows for faster mixing as it allows for the fluid components to stretch and fold much sooner along the flow direction. This allows to achieve full mixing within a much smaller channel length.

Microfluidics offers the potential for rapid and efficient analysis of DNA and proteins at a lower cost then traditional analysis. This is perhaps one of the most widely used commercial applications of microfluidics and has recently been seen most prominently in SARS-CoV-2 and other immunology testing tasks.

In soft robots, speed increases as body mass increases with the exception of robots using magnetic force actuation.

Toon and Pollack designed a model which gave global averages for the size distribution, chemical composition, and optical opaqueness of aerosols in the troposphere and stratosphere.

Prior studies conducted by Vogtmann et al, Hu et al, and Pierre et al. have embedded permanent magnets into the soft robot that allow for the generation of a magnetic field.

This actuation method allows for faster movement, but the robot developed by Hu et al has a top speed (213 mm/s) that is still one-fourth of the robot presented in this work.

In their research, Damme and Van Dooren use computer simulations to investigate a mouse's chance to escape predation by varying speed and body size. The authors conclude that relative speed (body lengths per second) is a more "ecologically relevant trait" because it better predicts the prey's ability to escape predators. This notion opposes previously published research, which considered absolute speed (meters per second) as the main predictor for prey vulnerability.

Dickinson et al found that most organisms (bi-pedal, multi-legged) use similar energy mechanisms for movement. In this article, our authors use piezoelectric material to mimic those movement patterns.

Previous studies have utilized PVDF films for various soft robot applications to lower driving voltage, increase actuation motion and improve moving speed.

Scientists, engineers, and clinicians need to work together to develop brain-computer interfaces (BCI) towards controlling artificial limbs with skill and speed approaching that of an able-bodied person.

The notable advancement in the article referenced here is the application of perovskite material within a monolithic tactile sensor. This material has properties of being ferroelectric and semiconducting which allows it to be made into a light harvesting, self-powered tactile sensor.

This paper draws inspiration from sensory (afferent) nerves to make flexible organic electronics. Afferent nerves carry sensations such as touch, pain, and temperature. The authors combined a pressure sensor, ring oscillator, and an ion gel-gated transistor to form an artificial mechanoreceptor. Their afferent nerve can detect movement, simultaneous pressure inputs, and distinguish braille characters.

This group fabricated inflammation-free, highly gas-permeable, ultrathin, lightweight and stretchable sensors that can be directly laminated onto human skin for long periods of time. Their unique device implemented nanomeshes, which aided in suppressing skin irritation and inflammation.

This publication describes a device that allows amputees to distinguish different textures using a sensorized artificial finger tip. This finger tip is unique because it includes a neuromorphic real-time mechano-neuro-transduction (MNT), a device that converts touch into nerve firing dynamics. These microsimulations are sent to an electrode, which is then directly attached to a nerve in a human subject. Both subjects with intact limbs and amputee subjects were able to distinguish differences in surface coarseness.

Microfluidic chemical reactors offer advantages such as reduced chemical consumption, high surface-area-to-volume ratios, and improved safety that make them superior to macroscopic reaction settings. These have been implemented in fluorination, tumor drug delivery, and various other applications.

The mixing efficiency (which is a function of angular displacement) can be optimized by changing the shape and the dimensions of the ridges.

Earlier studies have discovered how these two parameters effect each other. The authors developed a model to predict the effect of each geometrical parameter on the mixing efficiency.

Satellite measurements have greatly expanded the availability of precision measurements of solar luminosity and other external factors that determine climatic conditions on Earth.

A model of melting sea ice was constructed to account for heat flow in and out of ice, seasonal snow variations, and movement of ice packs. This model was used to predict the effects of a warming atmosphere on the Arctic Ocean.

Climatic conditions thousands of years ago have been studied extensively by combining geological evidence with computational climate models.

Global temperature trends are affected by a large number of factors on short time scales. This variation from year to year can obscure long-term trends until they grow sufficiently large to rise above the noise. Statistical methods like these can be used to predict such trends and estimate when they will be clearly visible.

The structure of sunspots was correlated with temperature variations on Earth. This correlation was argued to be due to sunspots reducing the amount of radiation emitted by the Sun.

The Mount Agung eruption provided an opportunity for researchers to collect data on stratospheric aerosols and compare the resulting climate effects with theoretical models. This work provided evidence for the viability of climate models for predicting atmospheric responses to large perturbations.

Early estimates of global cooling underrepresented climate trends in the Southern Hemisphere. Better data collection and analysis of data from stations south of the equator helped to correct these calculations.

Chlorofluorocarbons (CFCs), previously used as refrigerants, were predicted to deplete stratospheric ozone by a series of rapid chain reactions. This effect was shown to be the primary cause of widespread ozone depletion, resulting in the adoption of the Montreal Protocol, which banned the use of CFCs globally in 1987.

Even chlorofluorocarbons, which are relatively low in abundance, have been estimated to have significant climate forcing effects.

Global temperature changes due to human modification of the land were estimated. These modifications include the clearing of forests, construction of settlements, and expansion of deserts.

Simple models based only on variation of solar radiation and volcanic eruptions agree well with other estimates of preindustrial temperatures, indicating that these factors contribute strongly to overall climate variation in the absence of forcing by greenhouse gases.

Historical global fuel consumption was used to estimate the amount of carbon dioxide in the atmosphere before reliable measurements were taken. This model estimates a concentration of 293 ppm in 1880.

Box diffusion models assume a well-mixed atmosphere and divide the ocean into surface and deep ocean boxes. Diffusion into the shallow ocean occurs much faster than diffusion into the deep ocean. These models outperform box models that only consider the ocean as a single reservoir.

Careful measurements of the radiation absorbed by different atmospheric gases have greatly improved the accuracy of climate models.

Radiative-convective models assume that the atmosphere maintains a balance between heating (by the surface and by condensation of water) and cooling (by radiation into space).

By studying asynchronous flight systems in flies, Dickinson and Tu concluded that the resonant properties of the thorax (the midsection of an insect) determine the contraction frequency of the muscles.

Light can be easily controlled with high resolution and light-based mechanisms have been used in order to avoid potentially invasive wires or electrodes, Wang et al. chooses to use light-driven hydrogel; Rogóz ̇ et al. utilizes liquid crystalline elastomers that change shape under light; Park et al. uses tissue engineering principles to engineer cells that respond to light cues. Still, these prior publications are unable to achieve speeds greater than 3.2 mm/s.

Designing soft robots capable of carrying large weights has been challenging so far because of their lack of rigid structures.

In order to mimic a hop-like pattern, Kagawa et al. have used the movement style and foot path of cockroaches. On a larger scale, researchers like Haldane et al. have chosen a small primate, galagos, as their model animal which is known for having the highest vertical jumping ability.

In this study, Full and Tu used a miniature force platform to measure the ground reaction forces of the American cockroach, Periplaneta americana. Using this method, the authors observed varying types of cockroach locomotion which they described as a bouncing gait, switching from quadrupedal and bipedal running.

Aguilar et. al define "robophysics" as the pursuit of principles of self-generated motion.

This paper describes the first stretchable energy-harvesting electronic-skin device that is capable of differentiating and generating energy from pressure, bending, and vibration. The device had a maximum pressure sensitivity of 1.5 kPa-1, which is higher than the previously reported stretchable capacitive pressure sensors.

This paper describes a flexible and transparent e-skin device that was achieved by combining silk-molded micro-patterned PDMS with single walled carbon nanotube ultra-thin films. This device has great pressure sensing performance, but it is a challenge to form large-scale and uniform e-skin with cost effective fabrication methods.

The notable advancement in the article referenced here is a stretchable prosthetic skin. The artificial skin made in this reference article had enhanced ability to sense stimuli in highly variable external environments. It also had the ability to sense skin moisture and temperature.

A nonmechanical pumping mechanism was developed to move nano-liter and pico-liter sized drops of fluid within microchannels. The described system heats one end of a droplet and creates surface tension that causes a pressure difference in the channel, resulting in droplet motion.

A snake-like channel with repeating C-shaped segments was developed to enhance passive fluid mixing. This design achieved significantly more thorough mixing compared to straight channels and square-wave channels.

To understand the impact of human-made substances on the ozone hole, researchers have been tracking the level of ozone-depleting substances in the atmosphere.

Due to the Montreal Protocol, levels of these substances have been declining.

Thus, researchers are investigating whether the ozone layer has begun to heal as a result of this decline.

It has been well established that human-made chemicals are the primary cause of the hole in the ozone layer. These chemicals are called ozone-depleting substances.

In reference 12, Solomon details the chemical process of ozone depletion in the atmosphere.

Ozone-depleting substances (ODS) had already been declining for many years prior to 2015. Thus, it is noteworthy that the hole in the Antarctic ozone layer would reach record size in 2015.

Why such a large hole was observed in 2015 when ODS have been on the decline is one of the key questions investigated in the current paper.

Hofmann et al. in Reference 3 used 10 years (1986-1996) of Antarctic ozone level measurements to show how ozone recovery occurs over time.

They show that before an increase in ozone levels occurs, the rate of ozone loss slows down over time.

They predicted that conclusive signs of Antarctic ozone layer healing could be detected as early as 2008.

While the current publication focuses on ozone depletion in the Antarctic, WMO/UNEP periodically reports the state of the ozone layers in the Arctic and in the Antarctic. The reports also provide updates on the levels of ozone-depleting substances over time.

A complex computational model was constructed that considers geography, seasonal variation, and the circulation of heat and water across the entire globe. When the carbon dioxide concentration is increased quickly, the model predicts substantial heating of the Earth's surface.

Modeling of the effect of various manmade gases in the atmosphere showed that many pollutants absorb radiation that would otherwise be emitted to space. This causes energy to build up in the lower atmosphere, causing warming at the surface.

The interactions between the atmosphere, ocean, and land were modeled. These calculations showed that increased fossil fuel consumption was a much larger contributor to carbon dioxide levels than deforestation.

The genome encodes sex in many vertebrates, including humans (e.g. XX chromosomes lead to female development and XY leads male development).

But for some organisms, the ambient environment determines sex. In most reptiles, as well as some amphibians and fish, the incubation temperature of eggs directly determines whether males or females will hatch.

Here is a diagram describing the developmental trajectory of temperature-dependent sex determination in T. scripta: https://ars.els-cdn.com/content/image/1-s2.0-S0303720711006083-gr1_lrg.jpg

A previous study identified temperature-specific Kdm6b expression changes in American alligator during gonad development.

This data supports the role of KDM6B in temperature-dependent sex determination across reptiles.

The authors previously found six genes that were enriched in T.scripta embryos at MPT compared to FPT.

Here, authors tested if KDM6B might affect the enrichment of these genes at MPT.

KDM6B has been shown to initiate demethylation at H3K27 in various models and systems. This demethylation is closely associated with activation of genes located near the sites of demethylation.

In 2017, authors in this laboratory optimized a technique to inhibit gene expression in T. scripta (turtle) embryos.

Short hairpin RNAs (shRNAs) target complementary messenger RNA molecules for degradation, which blocks the target RNA from being able to make protein. The authors use a virus, called lentivirus, to carry and integrate RNA into the cells. This introduces the shRNA into the embryo while it is still in the egg (in ovo).

The authors originally sequenced the total RNA in turtle embryos at male- and female-producing temperatures (MPT and FPT) to identify differences in transcripts that may contribute to sex development.

Kdm6b was one of six transcripts that was consistently higher at MPT compared to FPT. Therefore, the authors decided to disrupt KDM6B in turtle embryos to test if it plays a role in sex development.

KDM6B (the protein) activates genes critical for early organism development, such as gonad specification and body patterning.

H3K27me3 is a histone mark that recruits repressive factors to that region of DNA, which leads to lower expression of nearby genes.

Methylation, or the addition of methyl groups to cytosines on DNA often leads to silencing of transcription of nearby genes.

Female-producing temperatures (FPT) specifically lead to removal of methylation and the addition of transcription-associated histone tail marks at the promoter for a gene that is critical to estrogen production during female sex determination. These marks were shown across reptiles, including turtles, alligators, and sea bass.

Similar intron retention was found in turtles and alligators, which again points to a role for KDM6B transcription in temperature-dependent sex determination across reptiles.

Another study on the Australian central bearded dragon showed that different introns in Kdm6b transcripts at high temperatures was sufficient to reverse the genetic sex determination.

This study found that phenotypical traits such as the size of a bird's beak and the fruit's diameter were strong factors that determined the likelihood of successful interactions, along with species abundance.

Dalsgaard and colleagues found that tropical areas have a lot of bird species that are obligate frugivores, meaning that they only eat fruited plants. Because fruit is their sole diet, these birds interact with a large variety of plants to ensure that they're consuming enough food to live.

This type of behavior is commonly associated with a low specialized network because the birds are not displaying any preference toward any particular plant(s).

Differences in geography affects the interaction patterns developed between species. Climate change, differences in species richness, and human impact were shown to dictate the types of networks that dominated those areas.

Bascompte, Jordano, and Olsen investigated coevolutionary interactions across a wide range of locations, measuring the levels of dependence between various species of plants and animals. They showed that most of these interactions are asymmetric, meaning that one species depends more heavily on the relationship than the other. This asymmetry supports high biodiversity and coexistence of multiple species in an ecosystem.

In a 2010 Hawaii statewide assessment of forest conditions and trends, a map illustrated that major vegetation types for multiple islands, especially O'ahu, experienced severe changes in comparison to before the arrival of humans.

The introduction of novel seed dispersers (aka birds) is an important factor regarding in the survival of native Hawaiian plant species. One study showed that the distribution of seeds from native plants is becoming increasingly dependent on not native but foreign birds. C. Chimera and D. Drake also found that these introduced birds tended to spread more seeds from non-native plants rather than native plants.

A mutualistic network is a web of beneficial partnerships between organisms. Disturbances to that relationship, like from one of the organisms becoming extinct, or by the intrusion of another species, can be harmful for the original partners of that relationship.

Brodie et al. reviews the concept of secondary extinction, the idea that the extinction of a species, caused by human activity, can lead to the loss of additional species.

Below is a diagram from the review depicting different types of secondary extinctions. Co-extinction is when the direct impact of humans (red arrow) leads to the loss of one species, causing the loss of another species, which can then cascade into a series of extinctions. Human activity (yellow arrows) also affects interactions between species (gray arrows).

In order to verify the model, Solomon et al. in Reference 24 compared the model's predictions to actual ozone abundance measurements.

After accounting for temperature variations and the particles released from volcanic eruptions, the model was in good agreement with actual measurements.

Models have demonstrated that aerosol particles released from volcanic eruptions can deplete the ozone layer.

Specifically, this modeling work demonstrated that the unusually large ozone hole in 1992 was caused by the eruption of Mount Pinatubo in 1991.

Human-made chemicals are primarily responsible for the formation of the hole in the ozone layer. However, other factors such as variations in weather conditions can produce variations in the size of the ozone hole from one year to the next.

Researchers in the field have worked to separate the human-made variations from those caused by other factors such as weather.

The WHO/UNEP scientific assessment reviews ozone hole data from numerous scientific studies.

While the 2015 assessment did not report healing in the polar regions, it did conclude that ozone levels had increased in other regions of the Earth since the year 2000.

Farman et al. were the first to publish the observation that a hole was forming in the Antarctic ozone layer, and they proposed that chemicals played a key role.

Professor Arnold's team demonstrates the first enzyme catalyzed carbenoid insertion into N-H bonds. The reaction proceeds in water with moderate yield.

This paper shows how directed evolution can be used to modify existing enzymes to carry out synthetically useful reactions. P450 BM3 enzymes were engineered to catalyze cyclopropanation of styrenes with very high diastereoselectivity and enantioselectivity.

By reviewing the most updated understanding of COVID-19 at the time, the authors identified a research gap concerned with the transmission patterns with and without interventions taken.

A better understanding of this aspect is necessary for evaluating the effectiveness of public health measures.

Three of these studies investigating the spreading patterns agree that human mobility is a critical factor in determining the spreading pattern of these infectious diseases, e.g., malaria, H5N1 influenza, etc.

These two articles summarized the measures introduced in the early stage of the outbreak.

Kraemer and the team showed that the mass control over transportation effectively restricted the spread of COVID-19.

Based on the RNA sequencing results, both works suggested that the novel coronavirus is closely related to a previously identified bat virus.

The two studies presented images and genome sequencing results of the novel coronavirus. The results agree on the identification of a new type of human-infecting betacoronavirus.

One of the reasons that DNA is typically easier to recover from ancient samples is that it is usually found as 2 strands twisted together making it more stable. Parvovirus B19 (B19V) has a genome that is a single strand instead of a double, meaning it typically would not last as long in remains. These authors recovered B19V DNA from remains that were between 0.5 and 6.9 thousand years old and demonstrated the virus has been associated with humans for thousands of years.

DNA from variola virus which causes smallpox has been recovered from a 300 year old Siberian mummy and a Lithuanian mummy from the 1600's.

DNA from hepatitis B virus has been recovered from skeletons found in Germany, a 16th century child mummy in Italy, and skeletons scanning a period of nearly 4,000 years from a variety of regions.

Some environments are more likely to preserve genetic material than others. The oldest DNA samples have been recovered from permafrost or regions where the ground remains permanently frozen. Other favorable environments include high salt concentrations, very dry environments like deserts, or environments with very low oxygen like bogs a type of wetland that contains large amounts of dead plant material.

Authors generated RNA data from wolf skins and liver tissue of an ancient wolf relative. This is the oldest RNA ever sequenced and the RNA was also tissue specific. This work demonstrates that RNA could possibly be recovered from tissues preserved over thousands of years.

In the supplement, the authors use previous studies to assert that while not formally established, the transmission of RPV spilling over into humans is much more likely than the opposite occurrence. They support this with 4 points.

1. Cattle and other hoofed animal populations were likely large enough to support RPV before human populations were large enough to support measles.
2. Older descriptions of RPV seem to exist than descriptions of measles.
3. Other viruses related to measles infect cattle, so it is more likely that RPV infected humans and became measles once rather than measles becoming a cattle virus several times.
4. Other Paramyxoviruses originated in domesticated animals and jumped to humans. Even with this evidence it cannot be ruled out that transmission from humans to cattle occurred.

Wertheim and Pond demonstrate the purifying selection or the removal of damaging alleles can make pathogens seem younger than they really are. Using models that take this phenomenon into account, they provide evidence that the origin of measles is older than previous estimates showed.

This book describes the history of outbreaks of disease from cattle in humans from the Roman empire to the 20th century.

Measles is only able to infect humans, while rinderpest virus is only able to infect cattle. This article provides evidence that outbreaks that occurred during the medieval period were a separate but related virus that was able to infect both cattle and people.

This study assessed regions where major settlements increased in size (upswept) or declined significantly and stayed down without rebounding (downswept). They identified 18 total significant upsweeps including those around 300 BCE.

This book provides information on measles expansion, consolidation, and retreat pre and post vaccine introduction within different geographical regions. They present mathematical models to describe the spread of measles epidemics and forecast geographical spread in various conditions.

Critical community size (CCS) is the smallest population size that can support the continued persistence of a human-to-human pathogen that is unable to infect animals. Bartlett estimated the critical community size to be around 250,000 using data from Manchester records. Black then used case reports from 19 island communities to establish a CCS of 500,000. Finally, Keeling and Greenfell used prevaccination data from England and Wales and estimated a CCS between 250,000 and 400,000.

Rhazes was a notable physician who authored more than 200 books and treatises or formal works on subjects like medicine and philosophy. His document "A Treatise on Smallpox and Measles" was the first book to distinguish between the two diseases.

RNA degrades more rapidly in the environment because it exists as a single strand while DNA is typically found in a double stranded structure. RNA is also made from ribose while DNA is made with deoxyribose which are two different sugars. The difference in the structure of these sugars makes RNA more susceptible to breaking down when it encounters water.

Muhlemann and colleges isolated DNA from ancient human parvovirus 19 and hepatitis B viruses to obtain genomes sequences. These sequences were then used to assess the historical relationship between these viruses and the human population and learn more about viral evolution.

These studies look at how evolutionary rates change over time and how these alterations can be accounted for in models. Ho and colleagues assert that rates of evolution change over time as a result of a variety of factors and refute the claims of Emerson and Hickerson. Aiewsakun and Katzourakis demonstrated that the time dependence in rate estimates applies for viruses. Accounting for rate variation in can provide more biologically realistic models.

Wolfe and colleagues assessed the origin of significant human infectious diseases. They found the origins of diseases varied based on climate and identified stages of a disease transitioning from an animal pathogen to a human pathogen. They found that diseases like measles from mild climates frequently originated from domestic animals like cattle.

The study shows the loss of axial methionine from cyt c. The same phenomenon was observed over a range of cyt orthologs. In Professor Arnold's work, the labile nature of methionine in cyt c is believed to be responsible for the improved efficacy of the C-Si bond forming biocatalyst.

In this study, Professor Arnold's group used protein-engineered variants of cytochrome P450 BM3 to bring about highly diastereoselective and enantioselective cyclopropanation reaction of styrenes from diazoester. Variant BM3-CIS was identified as a competent cyclopropanation catalyst. It exhibits a strong preference for the cis product and forms both diastereomers over 90% ee and is as stable as the wild-type enzyme. P450 BM3 works on a wide range of substrates with both electron-donating and electron-withdrawing substituents in styrene.

Measles is easily confused with smallpox because they both cause rash and fever. Distinguishing smallpox and measles is no longer a problem since smallpox has been eradicated.

While fixing with formalin preserves biological samples, it causes cross-linking or the chemical joining of molecules. These chemical bonds interfere with the sequencing process. Treating the tissue with heat before purifying the genetic material helps to fix this problem.

Normally depicted as the "tree of life" (shown below), the phylogenetic tree traces the genetic lineage of organisms over time. Two species share a phylogenetic relationship when they share a common ancestor. An example of a phylogenetic tree can be found at https://www.nationalgeographic.org/media/tree-life/

The authors of the cited paper found that phylogenetic relationships can influence the type of networks species build and explain the type of species involved in these interactions.

Electrochemical analysis revealed the loss of methionine from a range of cytochrome proteins.

Administering anti-CTLA-4 treatment in the absence of a tumor causes T cell responses to slow down. At the time this paper was published, it was not clear why this was the case.

The absence of CTLA-4 results in out-of-control cell division of T cells. Even though CTLA-4 is an inhibitory receptor, it is needed to produce the right balance of T cell activation, and its complete absence can be dangerous to organisms.

Using antibodies, scientists can induce dimerization of the receptor CTLA-4. Dimerization, a process whereby two similar molecules come together to form a single structure, is often the cause of signaling through a receptor. This experiment shows that the effect of CTLA-4 signaling is inhibition of T cell activation and expansion.

Mueller, Jenkins, and Schwartz summarize the models proposed by several scientists to explain why T cells only respond to foreign invaders and not to peptide-MHC on healthy cells. They summarize it as the "two-signal model of T-cell activation," whereby there must be another signal necessary for T cells to be activated.

This paper discusses that OROS controlled-release devices showed a low occurance of any significant GI events. When used correctly, extended-release products provide substantial therapeutic and convenience benefits without additional risk. Their small size allows for easy ingestion without significant difficulties

Specifically, this paper shows that the exact geometry of highly domed terrestrial species is close to optimal for self-righting, and the shell's shape is the predominant factor of their ability to flip back. This study illustrates how evolution solved a far-from-trivial geometrical problem

The conclusion from these sources is that most of the technologies in clinical trials are small scale and not groundbreaking. Even the more clinically advanced oral drugs examples of oral bioavailability appear to produce oral bioavailability values of only 1–2% and are, therefore, only currently suitable for a limited range of drugs.

demonstrated proof‐of‐concept experiments in swine that microneedle‐based delivery has the capacity for improved bioavailability of a biologically active macromolecule. Moreover, the paper shows that microneedle‐containing devices can be passed and excreted from the GI tract safely. These findings strongly support the success of implementation of microneedle technology for use in the GI tract.

No perforations (injuries) caused by the examination during 1210 upper endoscopies that were performed as part of this trial conducted by gastroenterologists (doctors that study the GI tract) Carr-Locke needle: https://www.steris.com/-/media/us-endoscopy-images/endoscope-devices/carr-locke_injection_needle_300.ashx

The gastrointestinal lining produces a wide variety of peptides which may contribute to protection from injury as well as repair after injury occurs. Restitution, the initial phase of mucosal repair, is accomplished by rapid moving of the epithelium to reestablish surface epithelial continuity (i.e. seal any injuries)

This study shows that orally administered devices could enable the systemic uptake of drugs by engineering around the physiological barriers present in the gastrointestinal (GI) tract. These designs must significantly increase drug bioavailability, deliver a correct dose and remain safe when taken frequently. This paper discusses how these physical methods stand to provide a solid set of alternatives to the classic hypodermic needle administration of drugs.

When surveyed, 208 women who were more than 2 years post-breast cancer diagnosis were surveyed about their preferences for daily oral tablets or monthly intramuscular injections. Sixty-three percent of these women preferred oral tablets. This preference has not changed overtime. In 1923, there was an experiment to see if insulin could be delivered orally via an alcoholic solution. It was found that a dose of insulin by mouth required double the dose of insulin administered through injection. That meant it would be much more expensive than the existing method. The oral dose was also much harder to control and unpredictable. Overall, it was determined that alcohol was not a sufficient medium to provide an oral dose of insulin.

This study showed that purification, or removal of other chemicals in the insulin solution, and treatment of insulin dependent diabetes mellitus (IDDM), or a disease often called sugar diabetes because the condition makes it difficult to convert food to energy. This leads to high sugar levels in the blood with intensive treatment (either multiple insulin injections per day or an external insulin pump) delayed the onset and slowed the progression of diabetic retinopathy (a disease of the eye caused by diabetes) when compared to conventional therapy.

Drugs that are orally administered must have various coatings to avoid being broken down within the gut. Although this does pose challenges, it is still promising to study and eventually utalize orally administered drugs for local GI targets.

The OROS osmotic (OSM) dosage form optimizes extended-release drug administration by controlling the rate of drug release for a predetermined time. OSM products include prescription medications for urology, Central Nervous System, and cardiovascular indications, as well as over-the-counter nasal/sinus congestion medications. This shows that the SOMA device is similar to previous devices, meaning it is a less risky device, because other products have been approved with similar materials.

This study evaluated the management of people with type 2 diabetes prescribed two or more oral medications, and/or insulin. It was seen that on average, the median time to insulin for patients prescribed multiple oral agents was 7.7 years. This showed that many people with type 2 diabetes received inadequate monitoring and had poor blood sugar control during the beginning of their treatments.

A soft robotic quadrupedal is a type of soft robot that has four appendages. These appendages can be contracted using a pneumatic network to allow for maneuverability.

Thermoelectrics convert heat into electrical energy. Electrical energy can be measured. Researchers can then use this information to decided how to change the IR signature. Electronic displays are devices that display images for visualization electronically, like a television. Each of these technologies, thermoelectrics and electronic displays, work independently. Electronic displays have no control over temperature. Meanwhile, thermoelectrics cannot display images.

Here, the author is demonstrating the novelty of his work. Rather than integrating both thermoelectrics and electronic displays onto the robot, a liquid network can do the work of each technology, greatly simplifying the soft robotic design.

The liquids used in the microfluidic channels of the device can be colored and heated (or cooled). Therefore, both temperature and color can be controlled simultaneously using one methodology.

Pneumatic networks, also known as PneuNets, are commonly used in soft robotics to illicit movement. Pneumatic simply means to operate by air or gas under pressure. PneuNets are networks of small channels embedded into soft robots that can be inflated or deflated with pressurized air to allow for maneuverability.

Here, researchers created two independent sets of microchannels inside of the robot. One set is filled with air and functions as the PneuNet, allowing the robot to move. The other set is filled with liquid and changes the color or temperature of the device; this set does not facilitate movement.

This link provides videos that demonstrate how a PneuNet functions: https://softroboticstoolkit.com/book/pneunets-bending-actuator

Fatemifar et al. (2013) showed that HMGA2 is associated with craniofacial features, such as the width of the eye region, the width of the lower part of the nose, and the height of the mid-brow prominence.

Ligon et al. (2005) had previously reported an 8-year-old boy with a shortened HMGA2 gene that exhibited widely-spaced eyes, a large head circumference, and premature dentition.

Zhou (1995) found that, in mice, mutant alleles sometimes arise from deleted DNA or from chromosomal inversions. When these mutations cause the protein Hmgi-c to inactivate and not be expressed in mice, the result is dwarfism. This protein is associated with the HMGA2 gene.

The previous tree from Lamichhaney and colleagues in 2015 showed that the initial split between warbler finches and other finches happened 900,000 years ago. Rapid divergence of ground and tree finches occurred 100,000 — 300,000 years ago.

Hybridization in finches has influenced the evolution of beak shape. Using phylogenetic studies along with genomic data allowed researchers to reveal some of the genetic variation that underlies finch beak diversity.

Lamichhaney et al. (2015) previously scanned the genomes of finch populations that were related but displayed different beak structures. They found that the ALX1 gene was a strong candidate for regulating the variation in beak morphology. ALX1 encodes a protein that is vital in developing structures from embryonic tissue that will form craniofacial structures.

Grant and Grant (1994) explored hybridization among finch species over 17 years. They concluded that hybrid traits were morphologically intermediate, which indicated the parent genes contributed to the offspring phenotype equally. Hybrids also varied more phenotypically.

Even though both were heritable, beak size seemed to be more important that body size because the beak's relationship to food acquisition.

Grant and Grant (2006) reported that the finch species Geospiza fortis diverged in beak size from one of its competitors, G. magnirostris. This divergence happened on an isolated Galapagos island 22 years after G. magnirostris arrived to share a habitat with G. fortis.

Abzhanov and colleagues (2004) analyzed various growth factors that were known to be expressed during craniofacial development of birds. When looking at Darwin's finch species, some factors showed no correlation whereas other factors showed a correlation with beak size, but not beak shape. However, researchers did find that the expression of the Bmp4 molecule had strong association with both beak size and shape.

Nogi and colleagues identified the role of gap junctions, which allow ions or other small molecules to move between cells, at the planarian amputation sites.

Shaw and colleagues determined the role of microtubules in the formation of gap junctions. The ability of cells to stick together (cell adhesion) is crucial to this formation.

Guger and colleagues identified that β-catenin may play a role in communication between cells via gap junctions.

This early (1800s) research on planarians provides an essential background for the regenerative capabilities of planaria. The observations from this research is essential for understanding planaria today.

Here, Morgan suggests that regeneration of a head versus a tail is related to the location of the amputation and the cells that reside there.

This research shows that β-catenin plays a role in all animal species studied including vertebrates and invertebrates, but how it is regulated in vertebrate animals may be different than in invertebrates. This is important to understanding stem cell regulation because it appears to regulated differently in planaria (invertebrate) than in humans (vertebrate).

In 2008, Bekar et al. demonstrated that the adenosine triphosphate (ATP) byproduct, adenosine, accumulated following deep brain stimulation. Adenosine would then activate adenosine A1 receptors which in turn depressed excitatory transmission in the thalamus and reduced tremors.