Structure-Guided Design and Biophysical Characterization of Novel Anti-HIV Reagents

Despite over 30 years of effort, an HIV-1 vaccine that elicits protective antibodies still does not exist. Recent clinical studies have identified that during natural infection about 20% of the population is capable of mounting a potent and protective antibody response. Closer inspection of these individuals reveal that a subset of these antibodies, recently termed potent VRC01-like (PVL), derive exclusively from a single human germline heavy chain gene. Induced clonal expansion of the B cell encoding this gene is the first step through which PVL antibodies may be elicited. Unfortunately, naturally occurring HIV gp120s fail to bind to this germline, and as a result cannot be used as the initial prime for a vaccine regimen. We have determined the crystal structure of an important germline antibody that is a promising target for vaccine design efforts, and have set out to engineer a more likely candidate using computationally-guided rational design.

In addition to prevention efforts on the side of vaccine design, recently characterized broadly neutralizing anti-HIV antibodies have excellent potential for use in gene therapy and passive immunotherapy. The separation distance between functional Fabs on an antibody is important due to the sparse distribution of envelop spikes on HIV compared to other viruses. We set out to build and characterize novel antibody architectures by incorporating structured linkers into the hinge region of an anti-HIV antibody b12. The goal was to observe whether these linkers increased the arm-span of the IgG dimer. When incorporated, flexible Gly4Ser repeats did not result in detectable extensions of the IgG antigen binding domains, by contrast to linkers including more rigid domains such as β2-microglobulin, Zn-α2-glycoprotein, and tetratricopeptide repeats (TPRs). This study adds an additional set of linkers with varying lengths and rigidities to the available linker repertoire, which may be useful for the modification and construction of antibodies and other fusion proteins.

A. An investigation of the relation between the tensile strength and (Brinell) hardness of non-ferrous alloys. B. A design of a fatigue testing machine for a college laboratory

[no abstract]

The principles involved in a factory cost system

Successful management has been defined as the art of spending money wisely and well. Profits may not be the end and all of business but they are certainly the test of practicality. Everything worth while should pay for itself. One proposal is no better than another, except as in the working-out it yields better results.

A colorimetric determination of hydrocyanic acid

The object of this investigation is to devise a rapid, fairly accurate, colorimetric analysis for HCN to be used in field work for determining instantaneous concentrations of the gas under fumigating canvas. A large amount of money is expended yearly by the citrus industry of this state in attempting to control and to eradicate the scale pests. Although fumigation with HCN has been practiced tor many years, the progress made has been anything but satisfactory. The greater portion of the work has always been carried on by contractors, who in a large number of cases have been very unscrupulous. The materials and labor are very expensive and the growers have been satisfied to adhere to beaten paths and hope for the best results on scale kill with the least attendant foliage injury. One familiar with fumigating, either from the grower's or the operator's viewpoint, knows that very widely varying results are obtained, even under what are apparently identical condition. Even after discounting for the dishonesty of some operators and the prejudices of the grower, there is still a large variance between desired or expected results and those actually obtained.

Design of an aerial tramway

An Aerial Tramway is a device for transporting material in receptacles over wire ropes supported at various elevations above the ground by means of posts or standards. Wire rope has been known for many centuries, and there is a drawing of a ropeway appearing in a book dated 1411.

Stress and load calculation for unknown building

Not available.

Efficiency and inefficiency in the operation of the Bureau of Power and Light of Los Angeles, California

In work of this nature it is advisable to state definitely the problem attempted in order that the reader may have a clear understanding of the object of the work undertaken. The problem involved is to determine the efficiency and inefficiency in the operation of the Bureau of Power and Light of Los Angeles, California, as it exists at the present time. This will be more on the order of a government investigation than a purely engineering thesis. An engineering thesis consists or reports based on experiments and tests, etc., while the present undertaking will consist of investigation of the facts concerning the organization, operation and conduct of the business of the Bureau of Power and Light. The facts presented were obtained from several sources: (1) the writer's knowledge of the business; (2) books written on municipal ownership; (3) reports published by the Bureau, and (4) personal interviews with men connected with the organization. I have endeavored to draw conclusions from the facts thus obtained, as to the present status of the Bureau of Power and Light.

A study of the proposed Santa Fe extension from the present Redondo Branch at El Segundo to Los Angeles Harbor

The Los Angeles Harbor at San Pedro with its natural advantages, and the big development of these now underway, will very soon be the key to the traffic routes of Southern California. The Atchison, Topeka, and Santa Fe railway company realizing this and, not wishing to be caught asleep, has planned to build a line from El Segundo to the harbor. The developments of the harbor are not the only developments taking place in these localities and the proposed new line is intended to include these also.

Formulas, tables, and graphs for trapezoidal reinforced concrete beams

Not available.

The Colorado River; a source of water and power for Los Angeles

The rapid growth and development of Los Angeles City and County has been one of the phenomena of the present age. The growth of a city from 50,600 to 576,000, an increase of over 1000% in thirty years is an unprecedented occurrence. It has given rise to a variety of problems of increasing magnitude.

Chief among these are: supply of food, water and shelter development of industry and markets, prevention and removal of downtown congestion and protection of life and property. These, of course, are the problems that any city must face. But in the case of a community which doubles its population every ten years, radical and heroic measures must often be taken.

The effect of earthquakes on reinforced concrete building design

The building under consideration was the Pasadena Furniture Building, on East Colorado St., Pasadena, California. It is a modern reinforced concrete building that may be classed as a warehouse of flat-slab construction.

Water conservation in the city of Pasadena

The object of this report will be to make a complete study of the water that is wasted in the storm drains of Pasadena and determine if there is any practical way of conserving this water.

Report of an investigation of a plan of elimination of grade crossings on the A.T. & S.F. Ry. in the city of Pasadena, California

The problem of the Atchison, Topeka, and Santa Fe railroad in Pasadena is a very dynamic one, as is readily recognized by engineers, city officials, and laymen. The route of the railroad was first laid out in the eighties and because of certain liberal concessions granted by the City of Pasadena, the right-of-way was located through Pasadena, despite the fact that the grade coming into the city either from Los Angeles or San Bernardino was enormous. Some years later, other transcontinental routes of the Santa Fe out of Los Angles were sought, and a right-of-way was obtained by way of Fullerton and Riverside to San Bernardino, where this route joins the one from Los Angeles through Pasadena. This route, however, is ten miles longer than the one through Pasadena, which means a considerable loss of time in a short diversion of approximately only sixty miles in length.

A comparison of the costs of operation of the motor bus, Birney safety car, and trolley bus on the local transportation routes in Pasadena

With the installation by the Pacific Electric Railway of a bus system in Pasadena to supplant most of its trolley lines, the problem of the comparison of the costs of the two systems naturally presented itself. The study here undertaken was originally started as just a comparison of the motor bus and Birney Safety Car, but as the work progressed it seemed advisable to include the trolley bus as well - a method of transportation that is comparatively new as far as development is concerned, but which seems to be finding increasing favor in the East.

Commercial testing of concrete

The material included within this report is the result of a series of tests of concrete specimens taken during the construction of various buildings in the cities of Pasadena and Los Angeles over a period of eight months.

The object of the problem is to determine the effect of the water ratio on the ultimate strength of the concrete as obtained from data observed and recorded from specimens taken from actual building practice rather than that from laboratory specimens made under ideal, or at least more nearly standard conditions.