Federal Incorporation

Since the beginning of our national history the Constitution, which is essentially the source of the law rather than its framework, has with more or less promptitude fulfilled the function of sanctioning new rules of action which will permit a fairly symmetrical institutional development in the face of the changing conditions of the environment in which the people live and think and act. Always the habits of the people are changing, always the situation facts are being modified, and the Constitution in its widest and truest meaning but provides the means whereby thru this flux the body of the people may crystallize its thought and usage into the forms of sanctioned law. It is only by such continual adaptation that the growth of a people becomes not abortive but wholesome and the interrelationship of its parts is kept from perversion

Federal Incorporation

We have traced in the foregoing part the principal cases bearing directly upon the federal power of incorporation. To gain a just perspective of the attitude the court may take upon the constitutionality of an act requiring uniform federal incorporation of all businesses engaged in interstate commerce it is necessary to complete our review by an examination of the trend of the court\u27s decisions involving other portions of the field of commerce regulation. The construction placed upon acts exerting other forms of regulation will not be so conclusive to our inquiry as the adjudication of the cases reviewed in the foregoing section, but by exhibiting the general trend of the judicial reasoning upon the subject of the commercial power it will provide us with a wider basis of judgment. We shall first examine the development of the Congressional control over foreign commerce, and following, its regulation of the various instrumentalities and objects of interstate commerce

Federal Incorporation

The course of development which rate regulation in general in this country passed through is well known. It may be briefly stated as follows: in the early cases it was held that when a state legislature prescribed a scale of maximum charges for a business affected with a public interest they substituted their will for the common law rule of reasonableness, and their determinations were held final and conclusive. This view was gradually modified so as to place a limitation upon the power of the law-making body in accordance with the view that the use and income of property, as well as its title and possession are protected by the Fifth Amendment and the Fourteenth Amendment against deprivation without due process of la

Patent Monopolies and Free Enterprise

Public policy has long recognized the intimate relation between a dynamic technology and a well-adjusted economy. Without experiment, industrial arts stagnate. Rightly understood, invention is synonymous with improvement in the industrial arts, and invention comes about only from experimenting. Not every inventor finds what he is looking for, true enough, or is looking for what he finds. But unless, consciously or unconsciously, he is seeking a new way to do something or a new combination of matter he will never discover anything. To encourage experiment and thus foster technical improvment is the avowed purpose of the American patent system. The men who wrote the Constitution did not mention patents but they did authorize Congress To promote the Progress of .. .useful Arts. The Constitution, moreover, specifies how this power, alone among the enumerated powers of Congress, shall be exercised. It limits congressional discretion in choice of means for accomplishing this end to . ..securing for limited Times to . ..Inventors the exclusive Right to their . . .Discoveries

Genetic Signatures in the Envelope Glycoproteins of HIV-1 that Associate with Broadly Neutralizing Antibodies

A steady increase in knowledge of the molecular and antigenic structure of the gp120 and gp41 HIV-1 envelope glycoproteins (Env) is yielding important new insights for vaccine design, but it has been difficult to translate this information to an immunogen that elicits broadly neutralizing antibodies. To help bridge this gap, we used phylogenetically corrected statistical methods to identify amino acid signature patterns in Envs derived from people who have made potently neutralizing antibodies, with the hypothesis that these Envs may share common features that would be useful for incorporation in a vaccine immunogen. Before attempting this, essentially as a control, we explored the utility of our computational methods for defining signatures of complex neutralization phenotypes by analyzing Env sequences from 251 clonal viruses that were differentially sensitive to neutralization by the well-characterized gp120-specific monoclonal antibody, b12. We identified ten b12-neutralization signatures, including seven either in the b12-binding surface of gp120 or in the V2 region of gp120 that have been previously shown to impact b12 sensitivity. A simple algorithm based on the b12 signature pattern was predictive of b12 sensitivity/resistance in an additional blinded panel of 57 viruses. Upon obtaining these reassuring outcomes, we went on to apply these same computational methods to define signature patterns in Env from HIV-1 infected individuals who had potent, broadly neutralizing responses. We analyzed a checkerboard-style neutralization dataset with sera from 69 HIV-1-infected individuals tested against a panel of 25 different Envs. Distinct clusters of sera with high and low neutralization potencies were identified. Six signature positions in Env sequences obtained from the 69 samples were found to be strongly associated with either the high or low potency responses. Five sites were in the CD4-induced coreceptor binding site of gp120, suggesting an important role for this region in the elicitation of broadly neutralizing antibody responses against HIV-1

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)). In total, 20 of the 49 waist-to-hip ratio adjusted for BMI loci show significant sexual dimorphism, 19 of which display a stronger effect in women. The identified loci were enriched for genes expressed in adipose tissue and for putative regulatory elements in adipocytes. Pathway analyses implicated adipogenesis, angiogenesis, transcriptional regulation and insulin resistance as processes affecting fat distribution, providing insight into potential pathophysiological mechanisms

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions

Federal Incorporation

We have traced in the foregoing part the principal cases bearing directly upon the federal power of incorporation. To gain a just perspective of the attitude the court may take upon the constitutionality of an act requiring uniform federal incorporation of all businesses engaged in interstate commerce it is necessary to complete our review by an examination of the trend of the court\u27s decisions involving other portions of the field of commerce regulation. The construction placed upon acts exerting other forms of regulation will not be so conclusive to our inquiry as the adjudication of the cases reviewed in the foregoing section, but by exhibiting the general trend of the judicial reasoning upon the subject of the commercial power it will provide us with a wider basis of judgment. We shall first examine the development of the Congressional control over foreign commerce, and following, its regulation of the various instrumentalities and objects of interstate commerce