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From Small Factory to Global Juggernaut

Behind the vision of Nathan Swartz, a new era in the world of casual footwear was born. Timberland has become famous for providing durable and dependable products in stylish and well-crafted designs. However, Timberland wasn't always the global juggernaut we all know and love today. In fact, it began in a small factory producing private label shoes for various brands under the name of Abington Shoe Company.

In 1955, Swartz had become full owner of Abington Shoe Company and turned it into a family business by bringing his sons on board. 1965 marks the year when the Swartz family got their big break, and everyday casual footwear took a massive leap into territories never thought possible. It was that year they developed injection-molding technology — a fusing process of the soles to the uppers. For the first time the stitching process was gone, and as a result, waterproof shoes were born.

Abington Shoe Company became the creator of the first waterproof boot, which at the time were called “Timberlands.” The boots were highly praised and their popularity soared. Before long, they became the backbone of the company. The boots were so huge that the company changed its name to what we currently know it as today.

The Urban Effect

Though the popularity of Timberland was steadily growing, it wasn't until the early-mid '90s that the company began soaring into iconic territory. In this time period, hip-hop artists began wearing the boots in music videos, at concerts, and even referencing them in their songs. Notorious B.I.G., among many others famed rappers, was known to frequently drop lyrics about his love for Timberlands. The younger generation recognized the style, comfort, and durability these boots could offer, which resulted in massive growth for Timberland.

As years progressed, Timberland began to expand beyond Myles Cap Toe Johnston amp; Murphy heDq5gCMa
, and into casual shoes, boat shoes , chukkas, and much more. However, despite their success in all type of footwear they bring to the market, the backbone of Timberland to this day remains the . Featuring leather or nubuck uppers, the Timberland 6” boot stands up to every day wear and tear, in nearly any condition.

Expand your casual shoe game. Score a pair of Timberlands today!

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McGovern Medical School

Stephanie A. Planque, PhD

Stephanie A. Planque, PhD (713) 500 - 5329

Education

Chemically Reactive Antibodies

Research Information

My goals are to study the beneficial and harmful functional effects of antibodies using covalently reactive electrophilic analogs of antigens. The electrophilic antigen analogs provide a new way to a. inactivate autoantibodies by forming irreversible antibody-antigen adducts; and b. induce antibodies with covalent and catalytic character. Antibodies to autoantigens and foreign antigens mediate, respectively, various pathogenic and beneficial effects. I discovered that most if not all antibodies express naturally-occurring, enzyme-like nucleophiles that react covalently with electrophilic chemical probes. The reactivity of the probes with the antibody nucleophilic site is accelerated by traditional noncovalent binding, which brings the electrophilic and nucleophilic groups into proximity with each other. A subpopulation of nucleophilic Abs expresses proteolytic activity, which can inactivate the antigen molecule permanently. I want to determine how the nucleophilicity can be exploited to inhibit harmful antibodies against autoantigens and activate the synthesis of beneficial antibodies against microbes and pathogenic molecules.

Together with my collaborators, I have discovered the innate recognition of the HIV coat protein gp120 by IgM and IgA class antibodies isolated from humans and mice without HIV infection. These antibodies hydrolyzed gp120 by a nucleophilic mechanism and neutralized HIV-1 with modest potency by recognizing the gp120 421-433 epitope, a conserved B cell superantigenic region that is also essential for HIV-1 attachment to host cell CD4 receptors. Unlike conventional antigens that bind to antibody complementarity determining regions, the 421-433 epitope bind the framework regions of these antibodies. An adaptive immune response to B cell superantigens is generally prohibited, as this class of molecules downregulates B cells. I have observed that IgAs from subjects with very prolonged HIV-1 infection displayed improved catalytic hydrolysis of gp120 and exceptionally potent and broad neutralization of diverse CCR5-dependent primary HIV isolates attributable to recognition of the 421-433 epitope. This indicates slow immunological bypass of the superantigenic character of gp120, opening the path to effective HIV vaccination.

Dr Paul, Dr Nishiyama and I have engineered electrophilic derivatives of gp120 as prototype vaccines against HIV infection. Data accumulated in the past 15 years have indicated that electrophilic gp120 derivatives induce antibodies with covalent and catalytic activities. Both types of activity derive from adaptively enhanced nucleophilic reactivity of the antibodies. Covalent antibodies can bind the antigen irreversibly, and by this means, permanently inactivate it. Catalytic antibodies permanently alter the target antigen structure. Moreover, their turnover capability allows catalytic antibodies to inactivate multiple antigen molecules. Our group has hypothesized that covalent immunization induces antibodies capable of more efficient inactivation of microbes compared to traditional immunization. My studies also suggests the potential of electrophilic immunogens to induce a productive antibody response to superantigenic epitopes that are otherwise poor targets of adaptive immunity. I participate in and provide leadership in developing an effective HIV vaccine through our new approach in the next few years.

Catalytic antibodies can potentially be employed as immunotherapeutic reagents. Together with my collaborators, I am studying the feasibility of developing immunotherapeutic catalytic antibodies for HIV infection, Alzheimer disease and senile systemic amyloidosis. I have isolated murine monoclonal antibodies after covalent immunization with electrophilic gp120 derivative. These monoclonal antibodies hydrolyze gp120 specifically and neutralize HIV potently. I have been awarded a phase I Small Business Technology Transfer grant application to develop these antibodies further. Similarly, I have isolated a catalytic anti-Ab(1-40) single chain antibody fragment from a phage-display library using electrophilic Ab(1-40) for selection. I continue providing leadership in the molecular and functional development of this antibody, including study of in vivo efficacy in clearing amyloid plaques in a U01 grant entitled “Efficacious and safe antibody catalyzed amyloid Beta clearance” for which I am a co-investigator. Finally, I am also a co-investigator in a small grant in which, I will try to isolate and characterize antibodies capable to specifically hydrolyze transthyretin aggregate, a hallmark of senile systemic amyloidosis that caused the death of supercentenarians.

I have demonstrated the inactivation of pathogenic Abs from Hemophilia A patients by means of nucleophile-electrophile pairing. Deficient factor VIII (FVIII) in HA subjects impairs blood coagulation. FVIII replacement therapy fails in 20-30% of HA patients due to production of anti-FVIII Abs. My approach consists of developing an electrophilic derivative of FVIII that can specifically and irreversibly inactivate the pathological anti-FVIII Abs. For evaluating in vivo efficacy, I intend to determine the pharmacokinetics of the electrophilic FVIII itself as well as its irreversible immune complex with antibodies in an animal model. In principle, development of electrophilic antigens for specific inactivation of autoantibodies could replace immunosuppressive drugs currently used for autoimmune disease treatment. The latter class of drugs induces a generalized inhibition of immune responses, and this leads to increased occurrence of infections. Inactivation of autoantibodies by electrophilic antigens, in contrast, holds the potential of neutralizing the specific subpopulation of antibodies with pathogenic effects without affecting the overall immune response.

Read my PubMed publications
Planque, S. A.
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Meg Dickey-Kurdziolek

Meg Dickey-Kurdziolek is a freelance UX Researcher based out of Pittsburgh, PA. All of her clients are startups, and she likes to write about her experiences in entrepreneurship and design on the User-Centered Startup blog. Meg is also a proud alumnus of Virginia Tech, where she received her Ph.D. in Human-Computer Interaction.

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