Well-defined Route Research Articles

NOAEL cancer therapy: a tumor targetable docetaxel-inorganic polymer nanohybrid prevents drug-induced neutropenia.

To date, cancer therapies largely consist of five pillars: surgery, radiation, chemotherapy, targeted therapy, and immunotherapy. Still, researchers are trying to innovate the current cancer therapies to pursue an ideal one without side effects. For developing such a therapy, we designed a chemically well-defined route to a PEG- and docetaxel (DTX)-conjugated inorganic polymer, polyphosphazene, named "polytaxel (PTX)" with a prolonged blood circulation time and tumor localization. Here, we conducted the proof-of-concept study of the ideal therapy in orthotopic and xenograft pancreatic cancer models. We found that the average tumor inhibition rates of PTX were similar to those of DTX without any DTX toxicity-related side effects, such as neutropenia and weight loss. In conclusion, PTX met the requirements of an ideal anticancer drug with high anticancer efficacy and 100% survival rate. PTX is expected to replace any existing anticancer therapies in clinical practice.

Everything and More: The Prospects of Whole Brain Emulation

Whole Brain Emulation (WBE) has been championed as the most promising, well-defined route to achieving both human-level artificial intelligence and superintelligence. It has even been touted as a viable route to achieving immortality through brain uploading. WBE is not a fringe theory: the doctrine of Computationalism in philosophy of mind lends credence to the in-principle feasibility of the idea, and the standing of the Human Connectome Project makes it appear to be feasible in practice. Computationalism is a popular, independently plausible theory, and Connectomics a well-funded empirical research program, so optimism about WBE is understandable. However, this optimism may be misplaced. This article argues that WBE is, at best, no more compelling than any of the other far-flung routes to achieving superintelligence. Similarly skeptical conclusions are found regarding immortality. The essay concludes with some positive considerations in favor of the Biological Theory of consciousness, as well as morals about the limits of Computationalism in both artificial intelligence and the philosophy of mind more generally.

Exo-Muscle: A Semi-Rigid Assistive Device for the Knee

In this work, we introduce the principle, design and mechatronics of Exo-Muscle, a novel assistive device for the knee joint. Different from the existing systems based on rigid exoskeleton structures or soft-tendon driven approaches, the proposed device leverages a new semi-rigid principle that explores the benefits of both rigid and soft systems. The use of a novel semi-rigid chain mechanism around the knee joint eliminates the presence of misalignment between the device and the knee joint center of rotation, while at the same time, it forms a well-defined route for the tendon. This results in more deterministic load compensation functionality compared to the fully soft systems. The proposed device can provide up to 38Nm assistive torque to the knee joint. In the experiment section, the device was successfully validated through a series of experiments demonstrating the capacity of the device to provide the target assistive functionality in the knee joint.

Electrodeposition of Stoichiometric CdTe from a Reusable Ionic Liquid Bath

Electrodeposition (ED) from ionic liquid (IL) medium is of much importance because a variety of architectures can be synthesized by IL assisted growth. However, these liquids are relatively new for the fabrication of compounds and alloys with a great control over the stoichiometry and thickness. In this regard a well-defined route needs to be established for their wider acceptance as greener alternatives to deposit materials like CdTe, CdS, CdSe, etc. via ED. In this article, we have discussed the prerequisites, tricks and methodology to develop stoichiometric CdTe thin films from IL medium with required thicknesses in a highly controlled way compared to conventional ED techniques. This method provides a greener alternative to aqueous electrolytes which are considered to be hazardous media for the ED of CdTe films. We have found that the required precursor ratio of Te:Cd can be lower down to 1:10 for [Bmim]Cl IL medium which is 1:1000 for the aqueous electrolytes. As-grown nanostructured CdTe films can be directly utilized for the devices like IR sensors, Schottky rectifiers and Solar cells without any post-annealing. Moreover, the aspect ratio of nanostructures can be tuned by changing the precursors’ ratio in IL bath. Nevertheless, IL can be reused multiple times to develop identical thin films which guarantee the low cost pathway.

WITHDRAWN: Electrodeposition of CdTe from a reusable ionic liquid bath

Abstract Electrodeposition (ED) from ionic liquid (IL) medium is of much importance due to a variety of architectures can be synthesized by IL assisted growth. However, these liquids are relatively new for the fabrication of compounds and alloys with a great control over the stoichiometry and thickness. In this regard a well-defined route needs to be established for their wider acceptance as greener alternatives to deposit materials like CdTe, CdS, CdSe, etc. via ED. In this MethodsX article, we have discussed the prerequisites, tricks and methodology to develop stoichiometric CdTe thin films from IL medium with required thicknesses in a highly controlled way compared to conventional ED techniques. This method provides a greener alternative to aqueous electrolytes which are considered to be hazardous media for the ED of CdTe films. We have found that the required precursor ratio of Te:Cd can be lower down to 1:10 for [Bmim]Cl IL medium which is 1:1000 for the aqueous electrolytes. As-grown nanostructured CdTe films can be directly utilized for the devices like IR sensors, schottky rectifiers and solar cells without any post-annealing. Moreover, the aspect ratio of nanostructures can be tuned by changing the precursors’ ratio in IL bath. Nevertheless, IL can be reused multiple times to develop identical thin films which guarantee the low cost pathway. • Nanostructured CdTe thin films • Low cost • Reuse of ionic liquid

A Critical Role of Extreme Atlantic Windstorms in Arctic Warming

Here we show that Atlantic windstorms of extreme category in northern winter tend to follow a well-defined route toward the Atlantic sector of Arctic, and that heat and moisture transported by these extreme storms significantly warm the Arctic. A positive North Atlantic Oscillation (NAO) condition and the associated intensified upper-level Atlantic jet provide favorable conditions for those extreme storm developments through enhanced vertical wind shear. These extreme windstorms lead to two discernible impacts on the Arctic: 1) enhanced poleward energy transport by moisture intrusion to the Arctic, which accompanies increased longwave downward radiation and 2) the occurrence of blocking-like patterns after the storm break-up. During these periods, significant Arctic warming was observed of a 10-fold increase versus normal and weak storms. The poleward deflections of extreme storms, and the Arctic warming driven by such storms, are well simulated in numerical experiments with ocean-atmosphere coupled models.

Metallurgical Aspects Affecting Thermomechanical Processing of Ti Based Microalloyed Steels

Thermomechanical processing is a well-defined route to achieve adequate combinations of strength/toughness for a wide range of applications. Inside this family, that based on accumulated strain in austenite followed by proper accelerated cooling strategies is probably one of the most selected. Usually this has been achieved with steels with Nb additions and other microalloying combinations. Recently, it has been observed an increase in the relevance of Ti as microalloying element. In addition to the classical approaches based on its availability to avoid grain growth, Ti provides, mainly in near-net-shape technologies, additional possibilities in relation to austenite conditioning and precipitation hardening. Multiple factors intervene simultaneously (solidification rates, Ti amount, Ti/N ratio, interaction with Nb...) leading nowadays, to important difficulties to properly predict its behavior. This manuscript focuses on some of these issues.

Nanocrystals: Why Do Silver and Gold N-Heterocyclic Carbene Precursors Behave Differently?

Synthesizing stable Au and Ag nanocrystals of narrow size distribution from metal-N-heterocyclic carbene (NHC) complexes remains a challenge, particularly in the case of Ag and when NHC ligands with no surfactant-like properties are used. The formation of nanocrystals by one-phase reduction of metal-NHCs (metal = Au, Ag) bearing common NHC ligands, namely 1,3-diethylbenzimidazol-2-ylidene (L(1)), 1,3-bis(mesityl)imidazol-2-ylidene (L(2)), and 1,3-bis(2,6-(i)Pr2C6H3)imidazol-2-ylidene (L(3)), is presented herein. We show that both Au and Ag nanocrystals displaying narrow size distribution can be formed by reduction with amine-boranes. The efficiency of the process and the average size and size distribution of the nanocrystals markedly depend on the nature of the metal and NHC ligand, on the sequence in the reactant addition (i.e., presence or absence of thiol during the reduction step), and on the presence or absence of oxygen. Dodecanethiol was introduced to produce stable nanocrystals associated with narrow size distributions. A specific reaction is observed with Ag-NHCs in the presence of thiols whereas Au-NHCs remain unchanged. Therefore, different organometallic species are involved in the reduction step to produce the seeds. This can be correlated to the lack of effect of NHCs on Ag nanocrystal size. In contrast, alteration of Au nanocrystal average size can be achieved with a NHC ligand of great steric bulk (L(3)). This demonstrates that a well-defined route for a given metal cannot be extended to another metal.

Differential expression of glycosaminoglycans and proteoglycans in the migratory pathway of the primordial germ cells of the mouse.

Primordial germ cells are an embryonic cell line that give rise to gametes in vertebrates. They originate outside the embryo proper and migrate by a well-defined route to the genital ridges. Proteoglycans and glycosaminoglycans have distinctive properties that affect many of the characteristics of the extracellular microenvironment of migratory pathways in a variety of developmental systems. The purpose of this work was to identify the proteoglycans and glycosaminoglycans that are spatially and temporally expressed in the migratory pathway of primordial germ cells. We showed that the expression of proteoglycans and glycosaminoglycans in the primordial germ cells migratory pathway changes according to the different phases of the migratory process. Some molecules such as chondroitin-0-sulfate, decorin, and biglycan are present only in certain phases of the migratory process of primordial germ cells. Heparan sulfate, chondroitin-6-sulfate, versican, perlecan, and syndecan-4, although exhibiting some variation in expression were detected during all phases of the migratory process. Our results indicate that the successive steps of primordial germ cell migration require a coordinated expression of proteoglycans and glycosaminoglycans, that should be present in appropriate levels and in specific areas of the embryo, and that the sequential expression of these extracellular matrix molecules is under a genetic program that appears to be common to a variety of cell types during embryonic development.

The role of the mitochondria in rat liver mixed function oxidation reactions

Recombination experiments indicate a complex role by the mitochondria in controlling drug biotransformation reactions. The use of liver slices and homogenates demonstrates that the effect of Krebs cycle intermediates on aminopyrine N-demethylation is not via an increase in NADH, but probably by a well-defined route from the mitochondria to the endoplasmic reticulum.

Patterned Walling in African Folk Building

In 1955 I spent some time at Kota Kota on the western shore of Lake Nyasa where I was fortunate to have as my guide Shehe Khalidi Bin-Amrani, a fine old Yao schoolmaster who, when I first met him, was busily teaching his pupils to read selections of the Koran from handled boards. His father, he told me, was born at Lindi, an important centre of the slave trade from where a well-defined trade route led to Lake Nyasa, but he eventually settled at Kota Kota and led the Arab traders in search of slaves. Khalidi Bin-Amrani actually took part in the last raids.

ON THE MECHANISM OF GLIOSIS IN ACQUIRED EPILEPSY

The theory of epilepsy expounded in the present paper is founded mainly upon structural considerations. The histological data have been interpreted largely from a functional point of view. The theory lays claim to some originality in two directions, in setting forth, namely, the properties of a typical epileptogenic focus in the cerebral cortex, and the nature of that change in cortical tissue which favors epileptic discharges. The characteristic feature of a typical prime focus is described as the separation of a normal cell-group from its normal control by other cell-groups and the impact upon the receptive surfaces of these normal cells of a steady, intimate, abnormal pressure—both segregation and compression effected by neuroglia overgrowth. That feature of cortical tissue which favors the spread of epileptic discharges is described as due to a simplification of cell arrangements, arising in the destruction of controlling elements with maintenance of motor elements. In the production of both prime foc...