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layout: post
title: Job Hunt is Over / What I learned
tags: [Hack Reactor, Job Hunt]
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And just like that, the job hunt is over.  I am excited to announce that I've accepted a software engineering position with [Fivestars](http://www.fivestars.com).  I am absolutely thrilled and think it will be a great match for both the company and myself.

Here are the things that I have learned through the job hunt process.  Hopefully, this is helpful for those of your going through it or heading into it.

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## It takes effort

The job search requires effort.  You have to put in the work to get the results.  Jobs don't apply for themselves.  In some ways, the whole process is about numbers.  The more jobs you apply for, the more phone screens you will get, which leads to more on-sites, which hopefully leads to offers.

Ulitmately, you want options so that you can be selective and choose a company or role that is the best fit.

## The people and culture matter

I have always cared about who I work with and what the culture is like.  I have explained it to others as the following:

We spend most of our waking life at work, let's make sure our work environment is as enjoyable as possible.

In the context of a job search, this means finding a great group of people to work with.  Every time you go on a job search, you have the ability to find people that you want to work with.  This goes back to my first point about giving yourself options.

## Interviews go both ways

Interviews are about companies finding out about you.  More importantly, however, interviews are a chance for you to interview the company.  I generally think this is the more important aspect of the interview.

This mindset also alleviates some nerves as I have a goal and I am focused on trying to get answers to my questions.  Interview guides will tell you to ask questions to show that you are interested in the company.  While this is true, I think this isn't about showing interest, you should genuinely be interested in getting informtion to answer this question for yourself:

Do I see myself working here?

## How does this fit with my career path?

When considering different companies, think about how it fits into your career path.  Where is it that you want to ultimately go?  What are you goals for learning?  Will this company help you get there?

These are the tips and questions that I have used to guide my job hunts over the years.  Feel free to ask questions or leave your own tips below.

redpajama_set_name: RedPajamaGithub


The site consisted of two bungalows and a row of shops. The small shops were empty by November 2007. New concrete forecourt has been laid and shops were re-built. New shops were all open by Mid-July 2008.
A new supermarket shop was built and opened in October 2013 and includes a small shop at the roadside which is currently a florist.


It appears that punters are truly enjoying the chance to bet on the next royal birth as bookmakers this week said that if the Duchess of Cambridge gives birth to a blonde daughter called Alice that it will cost them upwards of half a million pounds.
According to Ladbrokes two people have bet more than £2,000 each on the baby being a girl and the betting has been so intense that the odds have dropped to 8/15 for a girl while a boy is now at 11/8.
Similarly, the name Alice is now so popular that the odds have been reduced to 5/4 while the next favourite name Elizabeth is at 6/1.
It is also possible to bet on the day that the baby will be born, every day from now until April 27th is at 10/1, and the baby's hair colour with blonde and brown at 6/4 and red and black at 5/1.


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Erasmus MC: University Medical Center Rotterdam /
Nature Communications /
Young, A.L. (Alexandra L.), Marinescu, R.V. (Razvan V.), Oxtoby, N.P. (Neil P.), M. Bocchetta (Martina), Yong, K. (Keir), Firth, N.C. (Nicholas C.), Cash, D.M. (David M.), D.L. Thomas (David L), Dick, K.M. (Katrina M.), Cardoso, J. (Jorge), et al. J.C. van Swieten (John), B. Borroni (Barbara), D. Galimberti (Daniela), M. Masellis (Mario), M.C. Tartaglia (Maria Carmela), J.B. Rowe (James), Graff, C. (Caroline), F. Tagliavini (Fabrizio), G.B. Frisoni (Giovanni B.), R. Laforce (Robert), E. Finger (Elizabeth), A. De Mendonça (Alexandre), S. Sorbi (Sandro), J.D. Warren (Jason), Crutch, S. (Sebastian), N.C. Fox (Nick), S. Ourselin (Sebastien), Schott, J.M. (Jonathan M.), J.D. Rohrer (Jonathan) and Alexander, D.C. (Daniel C.)
Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference
Nature Communications , Volume 9 - Issue 1 p. 4273
The heterogeneity of neurodegenerative diseases is a key confound to disease understanding and treatment development, as study cohorts typically include multiple phenotypes on distinct disease trajectories. Here we introduce a machine-learning technique-Subtype and Stage Inference (SuStaIn)-able to uncover data-driven disease phenotypes with distinct temporal progression patterns, from widely available cross-sectional patient studies. Results from imaging studies in two neurodegenerative diseases reveal subgroups and their distinct trajectories of regional neurodegeneration. In genetic frontotemporal dementia, SuStaIn identifies genotypes from imaging alone, validating its ability to identify subtypes; further the technique reveals within-genotype heterogeneity. In Alzheimer's disease, SuStaIn uncovers three subtypes, uniquely characterising their temporal complexity. SuStaIn provides fine-grained patient stratification, which substantially enhances the ability to predict conversion between diagnostic categories over standard models that ignore subtype (p = 7.18 × 10-4) or temporal stage (p = 3.96 × 10-5). SuStaIn offers new promise for enabling disease subtype discovery and precision medicine.
Persistent URL doi.org/10.1038/s41467-018-05892-0, hdl.handle.net/1765/111144
Journal Nature Communications
Organisation Erasmus MC: University Medical Center Rotterdam
Young, A.L. (Alexandra L.), Marinescu, R.V. (Razvan V.), Oxtoby, N.P. (Neil P.), Bocchetta, M, Yong, K. (Keir), Firth, N.C. (Nicholas C.), … Alexander, D.C. (Daniel C.). (2018). Uncovering the heterogeneity and temporal complexity of neurodegenerative diseases with Subtype and Stage Inference. Nature Communications, 9(1). doi:10.1038/s41467-018-05892-0

redpajama_set_name: RedPajamaCommonCrawl


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Jul 30, 2012 04:47 PM EST
Warner Bros Looking Into A Shining Prequel
It's strongly rumored that Warner Bros are 'quietly exploring the possibility' of making a prequel to Stanley Kubrick's horror movie The Shining.
A spokesman for the studio told the LA Times that the project is 'at a very early stage'.
The prequel is thought to center on caretaker Jack Torrance before his time at the Overlook Hotel. Torrance the caretaker played by Jack Nicholson in the 1980 original, takes his family to the hotel for the winter, where, in the isolation he descends into madness.
Also rumored to be on the project is writer and producer Laeta Kalogridis, who has worked on both Avatar and Shutter Island with both James Cameron and Martin Scorsese in the past.
The Shining was adapted from the Stephen King novel of the same name, and is regarded as a classic by many horror fans.
Filed Under: warner bros, the shining


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Play ball: AQ softball set to continue success
By The Saint on March 21, 2018 • ( Leave a comment )
Story by Sam Kaser, Staff Writer
Image courtesy of aqsaints.com
The grass is becoming greener, and to the Aquinas Softball team that means it's time to begin the regular season.
The Saints are off to a hot start to the 2017-18 campaign, going 20-8 in their first 28 contests. The winning record still remains at 42, set in the 2000 and 2001 seasons, but the girls are gunning for that mark with earnest. Spring Break found the squad in Tucson, Ariz. to play 15 games in six days in an invitational tournament. The group tallied 12 wins in that stretch, and come home to Grand Rapids ready to continue their winning ways.
The team brings three seniors to the plate this year in Alex Forsythe, Brooke Senkbeil and Morgan Giddings. Forsythe has logged a .341 batting average over her 28 regular season games (excluding the Tucson Invitational), with 16 RBIs and 12 runs scored. Senkbeil, who rotates between outfield and catcher in the field, will look to improve upon her already impressive .298 batting average as the season rolls on. Giddings, the team's starting third baseman, has put up an solid .326 average, with 24 RBIs and eight doubles.
Along with core senior leadership doing their part, second year head coach Brad Koch continues to instill his winning mentality early in his tenure. After beginning his time with the program in 2008, Koch has worked his way to becoming the bench boss for the Saints. He has posted an incredible 55-21-1 record over his year and a half at the helm.
Alongside Coach Koch are assistants Jim Elliott and Jacki Plough, both in their ninth season. Mel Shephard enters her second season with the program, while Robert Dunham and Todd Johnston find themselves behind the bench for the first time at Aquinas.
Looking at the year ahead for the team, they were ranked in the preseason as the number one team in their division, and will seek realization on that mark with a talented group. Conference play begins on March 31 as the team will travel southeast to take on Rochester College. They will have a lengthy home stand in mid-April, as they host four teams for eight games in total.
The season looks bright for Koch's group, and the start has been everything it needs to be in order to search for that elusive 43rd win. With a strong core of leadership, and a confident group altogether, anything is possible for this year's team.
Tagged as: AQ, Softball
"Onward and Upward" panel discusses women in higher education
Crepes and coffee: a visit to Brown Butter


The Bachelor of Arts Degree in Applied Behaviour Analysis – Autism is a highly sought after and unique degree.
This baccalaureate program blends rigorous academic training and professional supervised experience.
Program graduates are eligible to sit for the exam immediately to become Board Certified Assistant Behavior Analysts (BCaBA).
Students who have completed 30 credits or a 30-credit credential may be considered for admission into year two of the program but must complete ABA 100, 101, 200 and 201. Students who have completed an Associate of Arts or Science, 60 credits, or a 60-credit credential plus documentation of at least 300 hours of BCBA-supervised ABA experience may be considered for admission into year three of the program and will be deemed to have met the requirements of ABA 100, 101, 200 and 201.


Unique parcel of Waterville Valley land zoned for Recreation. A beautiful and scenic area. Long border on Mad River East Branch. Ideal location for many creative recreational uses. Ski/hike/bike trails and flats. Angler's paradise! Riverfront beach. WV Zoning ordinance and potential use ideas attached as documents. Portions of this parcel were formerly used as town landfill/disposal area.


Solitaere ($0.99 → Free, 9.4 MB): Play a hand of cards whenever you have a spare moment with Solitaere. It's for fans of the Klondike variant.
WidgeTunes ($0.99 → Free, 1.0 MB): Choose and play your favorite tunes from within Today view with WidgeTunes. It's the ideal app for those who have a ton of music stored locally.
YoWindow Weather ($2.99 → Free, 42.5 MB): Have a look out the window to see what the conditions are like with this fun weather app. YoWindow is ideal for anyone looking for more than just a list of temperatures from their weather app.
Animal Math Games for Kids in Pre-K, Kindergarten and 1st Grade Learning Numbers, Counting, Addition and Subtraction Premium ($3.99 → Free, 34.1 MB): Your little ones can join Emma, the great math explorer, on a journey to guide her animal friends home in this educational game. It's for parents with children in preschool and first grade.
Star Rover HD – Stargazing and Night Sky Watching ($1.99 → Free, 35.5 MB): An app that turns your iPad into a portable planetarium. It's ideal for aspiring astronomers.


60%55°42°Night - Clear. Winds variable. The overnight low will be 45 °F (7.2 °C).Partly cloudy with a high of 55 °F (12.8 °C) and a 60% chance of precipitation. Winds variable at 4 to 12 mph (6.4 to 19.3 kph).
35%61°40°Scattered showers today with a high of 61 °F (16.1 °C) and a low of 40 °F (4.4 °C). There is a 35% chance of precipitation.
Today - Partly cloudy with a high of 55 °F (12.8 °C) and a 60% chance of precipitation. Winds variable at 4 to 12 mph (6.4 to 19.3 kph).


The Center for Fundamental Theory of the Institute for Gravitation and the Cosmos at Penn State University is organizing a 3-day workshop titled "Supergravity and M/Superstring Theory in the Ultraviolet and Double Copy" during the period September 6-8, 2018. This workshop will bring together experts in supergravity, M/superstring theory and amplitudes working on unraveling the high energy behavior of supergravity theories in various dimensions and related topics.
The workshop will be held in 320 Whitmore Lab on the Penn State University Park campus beginning Thursday, September 6 and concluding Saturday, September 8, 2018.
There is no registration fee; however, each participant must register in advance by sending an email to Randi Neshteruk at rxh1@psu.edu with the following information: Name, institutional affiliation, and professional status (faculty, post doc, graduate student). Registration deadline: September 1, 2018.


How can you better harness the power of the Millennials - and, in fact, every employee you lead? The toughest part of being a leader today is understanding what drives and motivates your people. In today's world, you are dealing with multiple generations whom all have different drivers and different needs! Companies with the highest employee engagement levels understand that yesterday's work environment is no longer enough to attract top talent. Contrast Consulting is hosting a 6 week Podcast series where we are interviewing leaders from around the globe to bring you insight into how to lead with this new Gen Challenge. Click below to listen to Session 3 of "A Voice at the Table!" with Carson O'Neill, and leave a comment telling us what your leadership challenges are.


The Volvo S60 is the epitome of an amazing concept that offers consumers high performance, superior luxury, and a quality that is second to none. Volvo has become a trademark of luxury cars and SUV's and the newer models are only some of the most impressive automobiles on the market today. The upcoming 2018 Volvo S60 is rumored to be one of the year's best luxury sedans, and we have all the reasons why.
The 2018 S60 is believed to bring back the amazing refined quality that has helped make Volvo synonymous with high-quality engineering. At first sight, it's hard to not notice the amazing craftsmanship that goes into each model, and with plenty to choose from it'll appeal to consumers of all interests.
This comprehensive preview of the new 2018 Volvo S60 specs, features, price, and release date takes a closer look at all models including the T5 and T6.
Volvo has made huge strides over the years with the S60 as the new innovative Inscription models have given it a breath of fresh air. With rumors on the 2018 Volvo S60 specs and features already coming in it seems like Volvo has no intentions with stopping anytime soon. This is great news for consumers as with a redesigned interior, more legroom in the back seat, and a sportier ride is on the way.
Standard and optional features will include alloy wheels, rear window sunshades, chrome exterior accents, rear park assist, interior accent lighting, Interior Air Quality system, lane assist guidance, crash avoidance front and rear sensors, panoramic moonroof, and much more.
The 2018 Volvo S60 AWD model will bring out the very best in off-road performance with Instant Traction control. Giving drivers an enhanced grip will significantly improve the handling both on-road and off-road.
Underneath the hood, the Volvo S60 engine is rumored to include a 2.0, turbocharged 2.5, and a more powerful 3.0-liter engine. We'll also see an 8 and 6 speed automatic and auto-manual transmission. Gas mileage will remain modest coming in around 27MPG/city and up to 40MPG/highway.
The wide array of models of 2018 S60 will give consumers numerous price options to choose from as the as the T5 will be the cheaper model while the T6 including the rumored T6 Platinum, T6 Polestar, T6 R-Design, and T6 R-Design Platinum will be the premium models. Below, we have detailed the expected launch price of all models for the 2018 Volvo S60.
The 2018 Volvo S60 release date could be announced as early as the spring of 2017, but we already believe it's likely to debut on the retail market in October of 2017. Of course, this is mere speculation as of this time, but pretty consistent to the leaks we're already hearing. It's also consistent with the launch of the previous year's model which have been debuting around the same time.
We'll continue to update you on all rumors and confirmations on the new 2018 S60 specs, features, price, and release date as soon as more comes available.


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CCR Focus Archive
COVID-19 & Cancer Resource Center
Lymphoma Collection
Myeloma Collection
Immunotherapy: Facts and Hopes
Report from the FDA
Approval Summary
Docetaxel in Combination with Prednisone for the Treatment of Androgen-Independent Hormone-Refractory Prostate Cancer
Ramzi Dagher, Ning Li, Sophia Abraham, Atiqur Rahman, Raji Sridhara and Richard Pazdur
Ramzi Dagher
Ning Li
Sophia Abraham
Atiqur Rahman
Raji Sridhara
Richard Pazdur
DOI: 10.1158/1078-0432.CCR-04-1402 Published December 2004
Purpose: Docetaxel, a taxane previously approved for the treatment of breast cancer and non–small cell lung cancer, was approved by the United States Food and Drug Administration on May 19, 2004 for use in combination with prednisone for the treatment of metastatic androgen-independent (hormone-refractory) prostate cancer. The purpose of this summary is to review the database supporting this approval.
Experimental Design: In a randomized, global study enrolling 1,006 patients, two schedules of docetaxel were compared with mitoxantrone + prednisone as follows: MTZ q 3w, mitoxantrone 12 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; TXT q 3w, docetaxel 75 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; and TXT qw, docetaxel 30 mg/m2 days 1, 8, 15, 22, and 29 every 6 weeks + prednisone 5 mg twice a day for a total of 5 cycles.
Results: There was a statistically significant overall survival advantage shown for the TXT q 3w arm over MTZ q 3w (median survival 18.9 months versus 16.5 months, P = 0.0094). No overall survival advantage was shown for TXT qw compared with MTZ q 3w. The most commonly occurring adverse events included anemia, neutropenia, infection, nausea, sensory neuropathy, fluid retention, alopecia, nail changes, diarrhea, and fatigue.
Conclusions: This report describes the Food and Drug Administration review supporting this first approval of a combination therapy for hormone-refractory prostate cancer based on demonstration of a survival benefit.
Docetaxel (Taxotere, Aventis Pharmaceuticals, Bridgewater, NJ) is an antineoplastic agent that acts by disrupting the microtubular network in cells that is essential for mitotic and interphase cellular functions. Docetaxel binds to free tubulin and promotes the assembly of tubulin into stable microtubules. Microtubules bundles without normal function are produced, and mitosis is inhibited. Docetaxel has been previously approved by the United States Food and Drug Administration (FDA) for locally advanced or metastatic breast cancer after anthracycline therapy, locally advanced or metastatic non–small-cell lung cancer after prior platinum-based chemotherapy, and for use in combination with cisplatin for newly diagnosed locally advanced or metastatic non–small cell lung cancer.
After development of metastatic hormone-refractory disease, prostate cancer is incurable, with median survival of 9 to 12 months (1 , 2) . Historically, no single agent or combination regimen has shown a survival benefit in this setting. In 1996, mitoxantrone administered in combination with prednisone was approved by the FDA for the palliative treatment of metastatic or locally advanced disease that had progressed on standard hormonal therapy. This approval was based on results of a randomized trial comparing mitoxantrone plus prednisone to prednisone alone. A total of 161 patients were randomized in this trial, which used palliative response as a primary endpoint (3 , 4) . A second randomized trial of mitoxantrone plus hydrocortisone versus hydrocortisone alone conducted by the Cancer and Leukemia Group B provided supportive evidence of a palliative effect (4) .
Docetaxel has been evaluated in single arm studies in hormone-refractory prostate cancer, either as a single dose every 3 weeks or a weekly regimen. Prostate-specific antigen (PSA) declines, and radiographic responses in those patients with bidimensionally measurable lesions were noted (5, 6, 7, 8, 9) .
TAX327, a global multicenter trial, was designed to evaluate two docetaxel schedules with prednisone compared with a control arm of mitoxantrone plus prednisone. The design and findings of this study are outlined below.
Patients were randomized to one of three treatments as follows:
The treatment plan is also outlined in Fig. 1⇓ .
Treatment schema.
MTZ q 3w.
Mitoxantrone 12 mg/m2 intravenously (day 1) as a 30-minute infusion every 21 days plus prednisone 5 mg orally twice daily for 10 cycles. Prednisone could be continued after completion of 10 cycles.
TXT q 3w.
Docetaxel 75 mg/m2 intravenously (day 1) as a 1-hour infusion every 21 days plus prednisone 5 mg orally twice daily for 10 cycles. Prednisone could be continued after completion of 10 cycles. Prophylactic dexamethasone 8 mg was to be administered orally at 12 hours, 3 hours and 1 hour before docetaxel.
TXT qw.
Docetaxel 30 mg/m2 intravenously as a 30-minute infusion on days 1, 8, 15, 22, and 29 every 6 weeks plus prednisone 5 mg orally twice daily for 5 cycles. Prednisone could be continued after completion of 5 cycles. Dexamethasone 8 mg was to be administered orally 1 hour before docetaxel infusion.
PATIENT POPULATION/DEMOGRAPHICS
The main protocol-specified inclusion criteria included histologically or cytologically proven adenocarcinoma of the prostate, metastatic disease unresponsive or refractory to hormone therapy (castration by orchiectomy and/or androgen blockade), and Karnofsky Performance Status ≥60. Except for estramustine monotherapy, prior chemotherapy was not allowed. Treatment with bisphosphonates had to be discontinued before randomization. Patients with symptomatic peripheral neuropathy grade ≥2 (National Cancer Institute Common Toxicity Criteria version 2.0), known brain or leptomeningeal involvement, or prior radiotherapy to >25% of bone marrow were excluded.
Age, race, Karnofsky performance status at baseline, staging, baseline PSA, and Gleason score are listed by distribution across the three study arms in Table 1⇓ . These seem to be evenly distributed across treatment groups. Approximately 84 to 89% of patients enrolled to each treatment arm had a baseline PSA ≥20. All of the patients had received prior hormonal therapy and/or surgery for hormonal control. Approximately half of all of the patients in each treatment had received prior radiation therapy, and ∼20% of the patients had received prior estramustine.
Baseline patient characteristics
The primary efficacy endpoint was survival, defined as time from randomization to the date of death from any cause. The primary analysis was done on the intent-to-treat population, consisting of all of the randomized patients. The study cutoff date for the primary analysis was March 24, 2003, the date on which the sponsor received notification of the 535th event. By that date, a total of 557 events had occurred. All of the subjects known to be alive at the cutoff date were censored either on the date of last assessment or on the cutoff date if the last contact had taken place subsequently.
Three simultaneous comparisons of overall survival were done with a modified Bonferroni adjustment to control for multiplicity (10) ; TXT q 3w versus control MTZ q 3w, TXT q w versus control MTZ q 3w, or the two pooled docetaxel treatment groups versus the control. The proposed nominal significance level for each comparison to MTZ q3w is as follows: Combined TXT groups, 0.04; TXT q 3w, 0.0175; and TXT q w, 0.0175. The primary analysis was to be considered positive if at least one of the three adjusted log-rank test comparisons was less than the prespecified nominal significance level for that comparison.
The stratified log-rank test (stratified on baseline pain and Karnofsky performance status) was prospectively specified as the primary means of determining if TXT q 3w and/or TXT q w increased overall survival compared with MTZ q 3w.
Overall survival was significantly superior in the TXT q3w group compared with the MTZ q 3w group (median survival 18.9 months versus 16.50 months, P = 0.0094). Overall survival was also significantly superior for the combined TXT groups compared with the MTZ q 3w group. Overall survival for the once weekly docetaxel arm was not statistically significantly different from that of the MTZ q 3w group. Results of the comparison of TXT q 3w to MTZ q 3w are summarized in Table 2⇓ , and the Kaplan-Meier survival curve for this comparison is depicted in Fig. 2⇓ .
Overall survival K-M curve TXTq3w versus MTZ.
Overall survival comparison of TXT q3w to MTZ q3w
Secondary endpoints included pain response rate and duration, PSA response rate and duration, tumor response, time-to-pain progression, time-to-PSA progression, and time-to-tumor progression. The FDA considered these secondary endpoints as exploratory and not supportive of a marketing claim for the following reasons: (a) there was no prespecified plan for adjustment for multiplicity or ordering of secondary endpoints; (b) only a portion of patients enrolled were evaluable for any one of these secondary endpoints; and (c) large proportions of patients were censored in the analyses for time-to-progression and response duration.
Docetaxel dose intensity was slightly lower in the weekly docetaxel regimen (96% of planned relative dose intensity, range 62 to 115%) versus the every 3 week regimen (98% of planned relative dose intensity, range 51 to 107%). These small differences are not likely to explain the difference found in efficacy outcome between the two docetaxel regimens.
Although >90% of patients enrolled on TAX327 had at least one reported treatment emergent adverse event, serious adverse events were less commonly reported in individual patients. Individual serious or life-threatening adverse events included infection, anemia, neutropenia, neuropathy, nausea, vomiting, diarrhea, and cardiac left ventricular dysfunction. Clinically relevant all grade and grade 3/4 treatment emergent adverse event observed in the TXTq3w and MTZ arms are presented in Table 3⇓ . Although allergic reactions (all grade) did occur more commonly on the TXTq3w arm, grade 3 or 4 events were observed in <1% of patients.
Clinically important treatment emergent adverse events
Neutropenia was the most commonly observed grade 3/4 cytopenia, occurring in 32% of patients in the TXT q 3w arm and 22% in the MTZ arm. Peripheral edema and weight gain were the major signs of fluid retention; severe or life-threatening fluid retention events were uncommon, occurring in <1% of patients across the three treatment arms. All grade cardiac left ventricular dysfunction events occurred more frequently on the MTZ q 3w arm compared with TXT q 3w (22.1% versus 9.6%), consistent with known cardiotoxicity of mitoxantrone, and grade 3/4 events occurred in 1.2% of patients on MTZ q 3w and 0.3% on TXT q 3w.
The incidence of deaths within 30 days of last treatment infusion was equally distributed across treatments: 3.3% for TXT q 3w, 3.3% for TXT q w, and 2.7% for MTZ q 3w. Most were attributed to malignant disease or "other" causes. Of the deaths occurring within 30 days of last infusion, one on the TXT q 3w arm and two on MTZ q 3w were attributed to drug toxicity.
Because prednisone is a known inducer of CYP3A4 and 3A5 (11) , the two enzymes involved in docetaxel metabolism, (12) the sponsor investigated any potential effect on docetaxel clearance by prednisone when both drugs were administered in combination. The pharmacokinetics of docetaxel were assessed in a subset of patients enrolled to TAX327. A total of 25 patients enrolled to TXT q 3w and 15 enrolled to TXT q w had blood samples collected for docetaxel pharmacokinetics with and without concomitant prednisone. Plasma docetaxel concentrations were measured with a validated liquid chromatography/mass spectroscopy method (13) . Plasma concentration/time data were analyzed with the previously developed population pharmacokinetics Nonlinear Mixed Effect Model (14 , 15) . No significant differences were observed between mean docetaxel clearance values when docetaxel was administered alone (day 1) or with prednisone (day 22) with either docetaxel dose/schedule. Although peak docetaxel concentrations were higher in patients receiving TXT q 3w than those receiving TXT q w, the small sample size of patients with pharmacokinetics evaluation does not allow correlation of peak docetaxel concentrations with efficacy outcomes.
Although several single agent and combination regimens have previously indicated antitumor activity in metastatic hormone-refractory prostate cancer and mitoxantrone/prednisone had shown a palliative effect, none have shown a survival benefit in this setting. The results of TAX327 show a survival benefit of docetaxel given with an every 3 weeks schedule plus prednisone in this setting.
The shown survival advantage was noted for the q3 week schedule and was not observed with the weekly docetaxel schedule. As discussed above, the small difference in relative dose intensity between the two docetaxel arms is not likely to provide an adequate explanation for this outcome. One hypothesis is that peak levels (Cmax) achieved on a relatively more intermittent basis may be more relevant to biological activity than overall exposure (area under the curve) in this setting. However, the small sample size of the subset population of TAX327 for which pharmacokinetics data were collected and analyzed precludes our ability to reach any conclusions in this regard.
Preliminary findings of a randomized study comparing docetaxel plus estramustine to mitoxantrone plus prednisone conducted by the Southwest Oncology Group (SWOG9916) also seem to show a survival benefit for a docetaxel-based combination regimen in the treatment of hormone-refractory prostate cancer. A median survival advantage of ∼2 months was observed for docetaxel/estramustine compared with the standard arm in this trial, which enrolled 770 patients (16, 17, 18) .
The findings reported herein provide a rationale for investigating the use of docetaxel in a less advanced and less heavily pretreated population of prostate cancer patients. These results also warrant additional investigation of novel agents in patients with hormone-refractory prostate cancer who have advanced disease and who progress after treatment with docetaxel-based therapy.
On May 19, 2004, the FDA approved docetaxel for use in combination with prednisone for the treatment of metastatic hormone-refractory prostate cancer based on a survival advantage shown over mitoxantrone plus prednisone in a global, multicenter clinical trial. The recommended dose of docetaxel is 75 mg/m2 every 3 weeks as a 1-hour infusion. Prednisone 5 mg orally twice a day is administered continuously. This represents the first approval of a chemotherapy regimen for the treatment of metastatic hormone-refractory prostate cancer based on demonstration of a survival benefit.
Requests for reprints: Ramzi N. Dagher, United States Food and Drug Administration, HFD-150, 5600 Fishers Lane, Rockville, Maryland 20857. Phone: (301) 827-1543; Fax: (301) 594-0499; E-mail: dagherr{at}cder.fda.gov
Revision received July 30, 2004.
Accepted August 5, 2004.
Pienta KJ, Sandler H, Javidan J, Sanda MG. Prostate cancer Pazdur R Coia LR Hoskins WJ Wagman LD eds. . Cancer management: a multidisciplinary approach 7th ed. 2003361-82. The Oncology Group New York
Ryan CJ, Small EJ. Advances in prostate cancer. Curr Opin Oncol 2004;16:242-6.
Fifty-first meeting of the Oncology Drugs Advisory Committee of FDA; Gaithersburg, Maryland. September 11, 1996.
Tannock IF, Osoba D, Stockler MR, et al Chemotherapy with mitoxantrone plus prednisone or prednisone alone for symptomatic hormone-resistant prostate cancer: a Canadian randomized trial with palliative end points. J Clin Oncol 1996;14:1756-64.
Picus J, Schultz M. Docetaxel as monotherapy in the treatment of hormone-refractory prostate cancer: preliminary results. Semin Oncol 1999;26(5 Suppl):14-8.
Friedland D, Cohen J, Miller R, Jr, et al A Phase II trial of Docetaxel in hormone-refractory prostate cancer: correlation of anti-tumor effect to phosphorylation of Bcl-2. Semin Oncol 1999;26(5 Suppl):19-23.
Beer TM, Pierce WC, Lowe BA, et al Phase II study of weekly Taxotere in symptomatic androgen-independent prostate cancer. Ann Oncol 2001;12:1273-79.
Petrioli R, Pozzessere D, Messinese S, et al Weekly low-dose Taxotere in advanced hormone-refractory prostate cancer subjects previously exposed to chemotherapy. Oncology (Basel) 2003;64:300-5.
Berry W, Dakhil S, Gregurich MA, et al Phase II trial of single-agent weekly Taxotere in hormone-refractory, symptomatic, metastatic carcinoma of the prostate. Semin Oncol 2001;28(15 Suppl):8-15.
Hochberg Y. A sharper Bonferroni procedure for multiple tests of significance. Biometrika 1988;75:800-2.
Pichard L, Fabre I, Daujat M, et al Effect of corticosteroids on the expression of cytochromes P450 and on cyclosporin A oxidase activity in primary cultures of human hepatocytes. Molecular Pharm 1992;41:1047-55.
Marre F, Sanderink GJ, de Sousa G, et al Hepatic biotransformation of docetaxel (Taxotere) in vitro: involvement of the CYP3A subfamily in humans. Cancer Res 1996;56:1296-302.
Wang LZ, Goh BC, Grigg ME, et al A rapid and sensitive liquid chromatography/tandem mass spectrometry method for determination of docetaxel in human plasma. Rapid Commun Mass Spectrom 2003;17:1548-52.
Bruno R, Hille D, Riva A, et al Population pharmacokinetics/pharmacodynamics (PK/PD) of docetaxel in phase 2 studies in subjects with cancer. J Clin Oncol 1998;16:187-96.
Bruno R, Vivier N, Veyrat-Follet C, Montay G, Rhodes GR. Population pharmacokinetics and pharmacokinetic-pharmacodynamic relationships for docetaxel. Investig New Drugs 2001;19:163-9.
Hussain M, Petrylak D, Fisher E, Tangen C, Crawford D. Docetaxel and estramustine versus mitoxantrone and prednisone for hormone-refractory prostate cancer: scientific basis and design of Southwest Oncology Group Study 9916. Semin Oncol 1999;26(5 Suppl 17):55-60.
Petrylak DP, Tangen C, Hussain M, et al SWOG 99–16: randomized phase III trial of docetaxel/estramustine versus mitoxantrone/prednisone in men with androgen-independent prostate cancer[abstract 3, plenary session]. Am Soc Clin Oncol Proc 2004;:
Petrylak DP. . Examination of end points in the SWOG Docetaxel trial 2004 Prostate Cancer Endpoints Workshop Bethesda, Maryland June 22,
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Science at the Cross Roads
A Summary of Dingle's Critique of Special Relativity
Paul Ballard, from Science at the Cross Roads by Professor Herbert Dingle
relativity: Either of two theories developed by Albert Einstein, the special theory of relativity, which requires that the laws of physics shall be the same as seen by any two different observers in uniform relative motion, and the general theory of relativity, which considers observers with relative acceleration and leads to a theory of gravitation. ( Collins Concise English Dictionary )
Professor H. Dingle, in his book Science at the Crossroads , was much concerned with highlighting the anomalies in Einstein's theory of Special Relativity. He chronicles his arguments with the scientific establishment and his growing disquiet with the way in which his views were ignored once he had drawn attention to problems in Relativity theory and become a heretic. Actually, Dingle was as much concerned with the attitude of leading physicists and scientific journals to scientific dissidents but here I shall concentrate on Dingle's criticisms of Relativity Theory.
The great majority of physical scientists, including practically all who conduct experiments in physics and are known to the world as scientific leaders confess, when faced with an irreconcilable criticism of Special Relativity, that they regard it as nonsense. They accept the theory because a few mathematical specialists in the subject say they should do so, or because they do not understand it at all but accept the theory as established by others and therefore a safe framework for their experiments. The response of specialists in this field is either complete silence or a variety of evasions couched in mystical language which serve to convince others that the theory is too abstruse for them to understand and that they may safely trust men with the mathematical talent to write confidently in profound terms.
Four Basic Misunderstandings: Misunderstanding One
Dingle outlines four basic misunderstandings which account for Special Relativity being accepted for so long despite its untenability. First, and most seriously, is the false conception of the relationship between mathematics and physics.
Galileo and Newton took observations as their starting point and used mathematics only as a tool to extract the maximum amount of information from their experiments, and as a means for expressing their new-found knowledge. The first example of the mastery instead of the servitude of mathematics in relation to physics came with Maxwell's theory of the electromagnetic field. Maxwell showed that in electromagnetism, Ampere's Law, expressed mathematically, did not satisfy the equation of continuity, but could be made to do so by a purely mathematical modification, which he assumed was the actual physical law. Since he knew of no physical relation which was represented by his equation he made the assumption that "displacement current existed in the dielectric, but which, unlike a conductor, could not carry electricity."
Faraday's 'Thoughts on Ray Vibrations' ( Philosophical Magazine , May 1846) illustrates that he planned to 'dismiss the ether' which was the basis of Maxwell's theory and endow each elementary light source with a system of rays extending indefinitely in all directions, the vibrations on the rays constituting light.
Einstein's Special Relativity, designed to conform to Maxwell's equations, could only do so by sacrificing the concept of the ether which was the basis of Maxwell's theory. Had Einstein first sought to bring Maxwell's equations into conformity with Faraday's, which amounted to a separate 'ether' for each atom instead of a single universal ether, he might have produced a theory which was not subject to flaws. Mathematical theories have become increasingly abstract, to the extent that multi-dimensional universes have been accepted as reality by some experimental physicists with no physical evidence of their existence. Why do mathematicians, whose formulae belong to the realm of pure thought, tell physicists to believe such absurdities and why do physicists believe them?
Misunderstanding Two
The second consideration derives from the multiplicity of meanings associated with the word time. Einstein's Special Relativity theory expounded in his 1905 paper has nothing to do with time in the sense of eternity; it is concerned with instants and durations (i.e. events and distances). Dingle states that the chief factor in creating the illusion that Relativity is unintelligible, or at least very difficult, is that it has something to say about the nature of time. Minkowski later introduced 'eternity' into his theory. Once the distinction between different forms of time is recognized, nearly all the literature on the subject of Relativity is seen to be in utter confusion. Writers such as Eddington in The Material Theory of Relativity (Cambridge University Press, 1930) for example, seem quite oblivious that time has different meanings and unconsciously oscillate between them.
Misunderstanding Three
The third of the most prominent sources of confusion that have led to the widespread illusion concerning Special Relativity is the substitution of observers for coordinate systems. In the literature on Relativity there is almost invariably a great deal about what different observers, in different states of motion, will observe. The impression is given that this is an essential feature of the theory. Writers have been prone to elevate the observer from a convenient accessory in explaining the theory's essentials to part of its essence. This distortion has misled not only general readers but many specialists as well. In Einstein's example of the station and the train, it can just as easily be supposed that the observer on the train is at rest while the observer on the platform is in motion.
All phenomena generally associated with Relativity – relative contraction of rods and distances when approaching light-speed, relative slowing down of clocks etc. – are not matters of observation, but are wholly concerned with coordinate systems. In Einstein's paper the 'observer' is not mentioned after the first two short sections right up to the end of the description. The picturesque image of the station and the train was used to introduce concepts which were at variance with those which had formerly been taken for granted.
Misunderstanding Four
The last of the errors permeating Relativity literature and the most effective in persuading experimental physicists that the theory must be right, notwithstanding their inability to make sense of it, is the literal interpretation of metaphors. This is best illustrated by the earliest of the supposed experimental verifications of Relativity – the increase in mass with velocity. It is the simplest example in an extremely complex matter, and in fact all supposed experimental verifications of Relativity can, with exactly the same justification, be used to verify Hendrik Antoon Lorentz's earlier and different theory. The compatibility of the mass/velocity relation with Lorentz's theory was pointed out by Lorentz himself, and shown to agree with observations already made before Einstein introduced his theory.
Dingle stresses that when we speak of the mass of an electron we cannot put the electron on a balance like a lump of lead and compare it with weights in the other pan. By the end of the nineteenth century electrons had been shown to be negative electricity with measurable properties, but thirty years later they were found to possess wave-like characteristics. The idea then arose that they were some sort of mist of electricity. Eddington probably gave the most candid description: "Something unknown doing we know not what." The velocity of the electron in the electron verification procedure resembles, for example, a car in motion no more than an electron resembles a lump of lead.
Einstein developed his theory to conform to the Maxwell-Lorentz electromagnetic theory, which he regarded as fact. Einstein's critique indicates that he believed the defect in Newton's system was that he had assumed, on inadequate grounds, that the time by the clock of a remote event had a unique value, but neglected to say how that value could be determined. Newton's kinematics assumed that the value at a distant event was the same as that shown by a terrestrial clock. Lorentz was the first to challenge this assumption, postulating that the motion of the clock through the ether changed its rate; but Einstein, discarding the ether, fell back on an assumption that the distant event had a unique instance of occurrence. Einstein claimed the right to determine such an instant in a form that conformed to existing electromagnetic theory without violating relativity of motion. It was a stroke of genius, but Einstein had not disproved Newton: Einstein's theory is not consistent because it requires each of two clocks to work steadily faster than the other, which is clearly impossible.
Non-Einsteinian Relativity
Before the end of the First World War Einstein's theory stood outside the mainstream. The conflict between Newtonian mechanics and Maxwell-Lorentz's electromagnetism was best illustrated by the Michelson-Morley experiment which split a beam of light into two parts which were sent, by means of mirrors, to and fro along two equal and perpendicular arms – one of which is aligned with the direction of movement of the Earth's orbit and one at right angles to the orbit. On returning to their starting point the light produced a pattern of dark and bright fringes. The fringes remained in the same position throughout the year both when the arm aligned with the Earth's orbit remained in its original position or, contrary to expectations, when the arm aligned in direction of movement was moved to a position at right angles to the orbit and the other arm was brought into alignment, i.e. when the position of the arms was reversed. This is contrary to the Maxwell-Lorentz theory, in which the velocity of light is independent of the motion of its source.
There are three possibilities: that the Maxwell-Lorentz theory is wrong; that Newtonian mechanics is wrong; or that there is some unknown effect of motion which has been overlooked. The first possibility has been ignored by everyone except Ritz. Einstein, as stated earlier, adopted possibility two, which, though not primarily for the purpose of explaining the experiment, was used for this purpose. The third possibility – that there is some neglected law of motion – was adopted by Fitzgerald, who proposed that a change occurred in the dimensions of bodies caused by their motion through the ether; for example, if the length of one of the arms in the light experiment changed, a shift in interference patterns would be expected.
Independently of this, in 1904 Lorentz proposed a much more comprehensive theory which, if valid, not only explained the null effect of the Michelson-Morley experiment but provided a supplement to Maxwell's theory. It implied that any experiment with material systems, carried out on bodies moving uniformly with respect to each other, would give exactly the same result; so that it would be impossible to tell, from an experiment confined to a body, whether the body was at rest or moving uniformly through the ether. Lorentz proposed that the movement of a material body through the ether produced a contraction in the direction of motion and a slowing down of all rhythmical processes by a factor of:
ß = (1 − v²c²)½
ß (alternatively µ) is used to denote the relative velocity coefficient between the two coordinate systems, where v is the velocity of a body and c the speed of light. Conventionally,
L = L′ß
where L and L' are the length of fixed and moving measuring rods in the two coordinate systems referred to below. Lorentz showed that if these physical effects were a reality the relationship between the coordinates (x,t) of an event referred to one coordinate system, and the coordinates (x,′t′) of the same event in a second coordinate system moving uniformly in the x direction relative to the first is given in terms of relative motion by:
x′ = x − vt
(1 − v²c²)½
t′ = t − vx/c²
(1 − v²/c²)½
These expressions became known as the Lorentz Transformations, and are as important in mathematical terms as Maxwell-Lorentz's electromagnetic theory is invariant to them; i.e. the Maxwell-Lorentz function remains unchanged when the Lorentz Transformation is applied. If, for x and t in these equations, we substitute the values given in the Lorentz Transformation, we obtain identical equations with x′ and t′ taking the place of x and t and with v changing to -v. This guaranteed that all measurements made on the two bodies, in uniform relative motion with velocity v or -v, when interpreted in terms of the theory, would be related in the same way so that no physical observations confined to one body could distinguish the motion of one body from the other. It would still be possible, by comparing observations on the two bodies, to detect their relative motion. This proposal became known as Lorentz's Relativity Theory.
Lorentz entitled his paper 'Michelson's Interference Experiment: Electromagnetic phenomena in a system moving with any velocity less than that of light' implying that, unlike the later theory of Einstein, his proposal did not prohibit velocities greater than the speed of light. Like Maxwell, Lorentz, in order to justify his transformation equations, postulated a physical effect of interaction between moving matter and ether. Einstein had no qualms about abolishing the ether and still retaining light waves whose properties were expressed by formulae meaningless without it; he was the first to discard verifiable physical laws altogether and propose a wholly mathematical theory. A more recent example of such a scheme was that proposed by Hugh Everett, who used Heisenberg's Uncertainty Principle of 1927 to argue that with every laboratory experiment, and also with every decision a person makes, the universe splits into additional universes.
The Twin Clock Paradox
Dingle argues that the basic principles of the theory are extremely simple. If you have two exactly similar and regular running clocks, A and B, in uniform regular motion (i.e. one is moving uniformly with respect to the other), the clocks must work at different rates. In mathematical terms dt and dt′ are the intervals, which are unequal, which the clocks record between the same events. dt and dt′ are related by the Lorentz Transformations. Hence one clock must work at a slower rate than the other.
The theory, however, provides no indication of which clock is slower and the question then arises: How is the slower-running clock distinguished? Either clock records the lesser time interval, depending on where the observer is situated, which is a contradiction. In response to Dingle's argument it has been claimed that the theory merely requires each clock to appear to move more slowly from the point of view of the other, but not actually do so in reality. This argument is ruled out by the theory's many applications (detailed in Part 3), by the fact that the theory would then be useless in practice, and by Einstein's own examples. After presenting a theory which took no account of gravitation, acceleration or any difference at all between the clocks except their relative motion, Einstein wrote that "We conclude that the balance clock at the equator must move more slowly, by a very small amount, than a precisely similar clock situated at one of the poles under otherwise identical conditions." Dingle asks: "What entitled Einstein to conclude from his theory that the equatorial and not the polar clock, worked more slowly?"
A paradox arises when two apparently contradictory conclusions, X and Y, follow from a premise P. It can be resolved if one of four instances can be shown, as follows: firstly, the conclusions are not, in fact, contradictory; secondly, the conclusion X does not follow; thirdly, the conclusion Y does not follow; fourthly, the premise P contains an internal contradiction so that X and Y follow from incompatible parts of the premise.
Dingle states it was almost inevitable that the clock paradox should arise from Einstein's 1905 paper, which described Special Relativity as follows: "If at the points A and B of the [coordinate system] K there are stationary clocks which, viewed in the stationary system are synchronous; and if the clock A is moved with velocity V along the line AB to B, then on its arrival at B, the two clocks no longer synchronize, but the clock moved from A to B lags behind the other which remained at B by ½tv²c², t′ being the time occupied in the journey from A to B." The stationary clock reading is denoted by t, v is the velocity of the body and c is the speed of light. That is to say, the time recorded on the clock moved from A to B is 50% less than the clock at B.
Einstein chose Y as the correct solution, but he did not disprove X. As both clocks are in relative motion clock B could equally be held to have lagged behind clock A. Nearly everyone accepts Y as the correct solution on diverse grounds ranging from the Doppler Effect, observation by external observers in various circumstances, the influence of the rest of the universe and electromagnetic considerations.
The argument to justify ignoring X utilizes the fact that if the clock moved from A to B returns to its starting point, it must undergo an acceleration, which removes the problem from the scope of the theory, because acceleration is only considered in General Relativity. However Y, like X, is drawn from Special Relativity so that if X is nullified, then so is Y. Secondly, Einstein's writings of this period indicate that he did not consider that acceleration affected the clock readings. Thirdly, the conclusion X is drawn from the postulate of Relativity alone, without the postulate of constant light velocity, and in his General Theory Einstein generalized the former postulate to cover both accelerated and uniform motion, so that if we accept the generalization, the acceleration cannot invalidate X.
Dingle was extremely concerned that the error in Relativity Theory would eventually lead to a major disaster. Twenty-six years after his book was published there is no sign that the scientific establishment has taken note of Dingle's critique and its implications for theoretical physics and nuclear research.
See further Science at the Cross Roads , Bristol: Western Printing Services, 1972
This is Part 1 of a series about Special Relativity and Lorentz and Dingle's ideas in particular. Comments are invited. paullb@totalserve.co.uk


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Prof. Erik Grumstrup (Dept. of Chemistry and Materials Science MSU) will kick off our fall seminar series with a presentation titled "Dynamics at the mesoscale: time resolved microscopy of chemical systems from 10^-3 to 10^5 daltons." 3:10 pm in the Byker Auditorium.
Ms. Ece Topuzlu will defend her Ph.D. in Biochemistry beginning with a seminar titled "Biochemical and Biophysical Characterization of Plastic Degrading Aromatic Polyesterases." Ece works in the laboraotry of Prof. Valérie Copié.3 pm in the Byker Auditorium.
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Ms. Emerald Ellis will present her fourth year graduate student seminar titled "Controlling Oxygen's Potential for Fun and Profit." Emerald is Ph.D student in Jen DuBois' Lab. 3:10 pm in the Byker Auditorium
Prof. Dong Wang (U of Montana) will present "High-valent Co2(μ-O)2 Diamond Core Complexes: New Bio-inspired Strategies for Aliphatic C-H Bond Activation." Byker Auditorium at 3:10 pm Prof. Sharon Neufeldt host.
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Dr. David Tyler (Department of Chemistry and Biochemistry, University of Oregon) will present "Homing Pigeons, Degradable Plastics, and Solvent Effects; How Caged Radical Pairs Impact Everyday Chemistry." Byker Auditorium at 3:10 pm. Prof. Mike Mock host.
How do homing pigeons navigate? How do we design plastics so they degrade after they are used? Why are solar energy conversion systems with donor and acceptor complexes so inefficient? Why do bonds break more readily if they are under mechanical stress? It turns out that radical cage effects are important in understanding the answers to these and numerous other practical questions involving chemical reactivity. In this seminar, I will introduce the concept of caged radical pairs, and then I will show why caged radical pairs are key intermediates in the systems mentioned above and in radical reactions, in general.
Mr. Jesse Peach will present "Making Sense of Complex Biological Fluids Using Mass Spectrometry" as part of his 4th year graduate student PhD requirement in Biochemistry. Jesse works in the lab of Prof. Brian Bothner.
Dr. Alan Weaver (U.S. Army Institute of Surgical Research, Fort Sam Houston, TX will present "Insights into Burn Wound Infection & the Post-Doctoral Experience in the U.S. Army Research Sector" in the Byker Auditorium at 3:00 pm. Alan graduate from our Department with a Ph.D in Biochemistry. Prof. Valerie Copie will host.
Ms. Amanda Fuchs will defend her PhD in Biochemistry beginning with a seminar titled "Quantitative 1H NMR Analyses of Immunometabolic Modulation in Human Macrophages." Amanda works in the lab of Prof. Valérie Copié. 3:10 pm in the Byker Auditorium.
Dr. May Nyman from Oregon State University will present "Building Materials from Molecular Clusters" in the Byker Auditorium at 3:10 pm. Prof. Nick Stadie will host.
Metal-oxo clusters are modular building blocks for materials via hydrolysis reactions and coordination chemistry. Landmark discoveries in cluster-based materials include zeolites and MOFs. Understanding and controlling solution phase reaction pathways from monomers to clusters to materials (and vice versa) will lead to new discoveries from across the periodic table, and most aspirational, the next new class of cluster-based materials.
I will present an overview of our studies of metal-oxo clusters and their importance in functional materials and understanding reaction pathways, beginning with an introduction to small-angle X-ray scattering as a primary tool in studying cluster systems. Time permitting, presented cluster systems will include; 1) The iron Keggin ion and its relevance to natural systems; 2) Diversifying Zr/Hf oxocluster chemistry with peroxide (and use in microelectronics); 3) Behavior of Nb-POMs around neutral pH; and 4) heterometallic U(IV) clusters and materials.
Nicholas J. Borys Department of Physics, Montana State University
Excitons in 2D Atomically Thin Semiconductors
Abstract: Transition metal dichalcogenide semiconductors, such as monolayer MoS2, are an emergent class of ultrathin thin semiconductors that are only three atomic layers thick yet host a rich suite of photophysical phenomena that provides new opportunities ranging from fundamental investigations of many-body physics to the development of new optoelectronic and quantum devices. In these atomically thin semiconductors, the absorption of light creates an "exciton," which is an excited electronic state composed of a negatively charged conduction band electron that is tightly bound to a positively charged valence band hole. Like molecules, excitons govern light-matter interactions such as absorption and emission in 2D semiconductors and are fundamental packets of energy that can be leveraged for next-generation technologies. Using time-resolved and nano-optical spectroscopy techniques to access excitonic physics at extreme length and time scales, a striking diversity of excitonic phenomena has been identified in these 2D materials. Building on previous results, our newest findings in these regimes highlight how exciton populations can be coerced into interacting to form bound states of multiple electrons and holes as well as how strain localizes excitons on length scales that are commensurate with their size. These new results demonstrate the exciting potential of monolayer semiconductors to be utilized for model optoelectronic and quantum devices with unique functionalities derived from 2D excitonic physics.
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Ms. Grace Purnell will defend her PhD in Chemistry beginning with a seminar titled "Unusual Isomerization Behavior of Organic Solutes at the Aqueous-Silica Interface." Byker Auditorium at 3 pm. Grace works in the lab of Professor Rob Walker.
Mr. Colin Miller will defend his PhD in Chemistry beginning with a seminar titled "Redox Homeostasis and Stress in Mouse Livers Lacking the NADPH-dependent Disulfide Reductase Systems." 2 pm in the Byker Auditorium. Profs. Mary Cloninger and Ed Schmidt are the advisors.
Prof. Takamitsu Kohzuma, Institute of Quantum Beam Science Institute, and the Frontier Research Center of Applied Atomic Sciences, Ibaraki University, Mito, Ibaraki will present
"The Strong Weak-Interaction in Protein"
Noncovalent weak interactions play important roles in biological systems [1]. In particular, such interactions in the second-coordination shell of metal ions in proteins modulate the structure and reactivity of the metal ion site in functionally significant ways.
Recently, we have demonstrated the perturbation of weak non-covalent interaction on the structure and properties of copper site in a blue copper protein, pseudoazurin (PAz) [2]. PAz is well known to work as an electron transfer protein to NO2- reductase and N2O reductase in denitrifying bacteria [3]. The weak interaction at Met16 with a copper coordinated histidine (His81) imidazole ring in the second coordination sphere provides significant effect not only for the PAz properties and local structure but also the whole protein stability [4].
In this lecture, I also would like to introduce the utilization of modern quantum beams involving Synchrotron X-ray, Neutron Beam, and Muon in bioinorganic chemistry.
K. Burley and G. A. Petsko, Science, 229, 23 (1985); O. Ymauchi, A. Odani, T. Kohzuma, H. Masuda, K. Toriumi, and K. Saito, Inog. Chem., 28, 4066-4068 (1989); T. Kohzuma, et al., J. Biol. Chem., 274, 11817-11823 (1999); R. F. Abdelhamid, Y. Obara, Y. Uchida, T. Kohzuma, D. M. Dooley, D. E. Brown, H. Hori, J. Biol. Inorg. Chem., 12, 165-173 (2007); D. Rokhsana, D. M. Dooley, R. K. Szilagyi, J. Am. Chem. Soc., 128, 15550-15551 (2006); A. Taborosi, T. Yamaguchi, A. Odani, O. Yamauchi, Bull. Chem. Soc. Jpn., in press.
Yamaguchi, K. Akao, A. Takashina, S. Asamura, M. Unno, R. K. Szilagyi, T. Kohzuma, RSC Adv., 6, 88358-88365 (2016); M. B. Fitzpatrick, Y. Obara, K. Fujita, D. E. Brown, D. M. Dooley, T. Kohzuma, R. S. Czernuszewicz, J. Bioinorg. Chem., 104, 250-260 (2010); T. Yamaguchi, J. Yano, Y. Vittal, Y. Nihei, H. Togashi, R. K. Szilagyi, T. Kohzuma, Bull. Chem. Soc. Jpn., 88, 1642-1652 (2015).
Kohzuma, S. Takase, S. Shidara, and S. Suzuki, Chem. Lett., 149-152(1993); K. Fujita, M. H.-Fujita, D. E. Brown, Y. Obara, F. Ijima, T. Kohzuma, D. M. Dooley, J. Inorg. Biochem., 115, 163-173 (2012)
F. Abdelhamid, Y. Obara, T. Kohzuma, J. Inorg. Biochem., 102, 1373- 1379 (2008); T. Yamaguchi, Y. Nihei, D. Southerlands, M. Stillman, T. Kohzuma, Protein Science, 1921-1931 (2017).
2 pm in ABB 138. Prof. Robert Szilagyi host.
Dr. Aaron Wright from Pacific Northwest National Lab will present "Cultivation- and Genome-Independent Functional Profiling of Microbiomes with Chemical Probes."
Abstract: We are developing and applying chemical probe approaches to characterize and quantify enzyme activities within environmental and host-associated microbial communities. Specifically, our probe-based methods do not require genomes or genome inferences nor microbial cultivation to assess specific functional activity of microbial cells in complex communities. In host-associated and environmental systems we are using our probe-based approaches to delineate how perturbations or exposures create metabolic susceptibilities and alter microbial functions, community physiology, and community structure. Our research is enabling the microbiome sciences community to move from functional inference to direct measurement. 3:10 pm in Byker. Prof. Roland Hatzenpichler is the host.
Ms. Sarah Hopfner will present her research in a graduate student seminar titled "Drug Development for Tuberculosis: Making Drugs that Shut Down the Backup Power." 3 pm in the Byker Auditorium. Professor Mary Cloninger is the research advisor.
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Dr. Sean Brady (Rockefeller University) will present "Watch Your Step, There Is New Chemistry Everywhere."
The characterization of biologically active small molecules (natural products) produced by easily cultured bacteria has been a rewarding avenue for identifying novel therapeutics as well as gaining insights into how bacteria interact with the world around them. Large-scale sequencing of bacterial genomic and metagenomic DNA indicates that this traditional pure culture-based approach to studying bacterial natural products has only provided access to a small fraction of the diverse metabolites encoded by environmental microbiomes. In particular, these studies suggest that in most environments, uncultured bacteria outnumber their cultured counterparts by at least two orders of magnitude. Although there appears to be no easy way to culture this collection of unstudied microorganisms, we have developed culture-independent methods to circumvent this discovery bottleneck, which involve the extraction, cloning and heterologous expression of bacterial biosynthetic gene clusters directly from environmental samples. The application of these methods to the identification of new antibiotics from the global soil microbiome as well as metabolites encoded by the human microbiome will be discussed. Prof. Roland Hatzenpichler is the host. 3:10 pm in the Byker.
CHMY and BCH 494 students will present their research starting at 1 pm. Each presentation will be aproximately 25 minutes. Students presenting are Luke MacHale (Robert Szilagyi advisor), Heath Weaver (Garrett Moraski advisor) and Brock Cone (Jovanka Voyich advisor).
Byker Auditorium
Ece Topuzlu will discuss her recent findings from her PhD dissertation in a seminar titled "Characterization and Engineering of MHETase, a Plastic Degrading Polyesterase." Ece completed all PhD degree requirements in September of 2019 but did some additioinal data collection and analysis for the past two months in the lab of Dr. Gregg Beckham at NREL. Ece's research advisor is Valérie Copié . Byker Auditorium at 3:10 pm
Abstract: Accumulation of synthetic plastics in the biosphere is leading to a global environmental crisis. In response, microbes are evolving strategies to convert man-made polymers into carbon and energy sources, and these systems offer a promising starting point to harness for biotechnological purposes towards plastics upcycling. To that end, Ideonella sakaiensis 201-F6 was recently reported to secrete a two-enzyme system to deconstruct the abundant synthetic polyester, polyethylene terephthalate (PET), to its constituent monomers for further catabolism. The PETase enzyme specifically breaks down the PET polymer, liberating mono-(2-hydroxyethyl) terephthalate (MHET), which is then cleaved to its constituent monomers, terephthalic acid and ethylene glycol, by MHETase. This talk will focus on the structure and function of MHETase. Crystal structured of MHETase solved at 1.6 Å reveals an α/β hydrolase fold with an additional lid domain. In addition, we have expressed and purified multiple mutants of MHETase and PETase to assess the function of the lid domain, and we have identified homologous enzymes from two other organisms also turnover MHET. Lastly, we have explored further into the synergistic reactions of PETase and MHETase together and constructed chimeras for assessing the optimum PET turnover. Taken together, these results offer new molecular-level insights into the two-enzyme system of I. sakaiensis in the breakdown of recalcitrant PET.
Graduate Student Seminar -Stella Impano (Joan Broderick Lab) 2 pm Byker
Graduate Student Seminar - Angela Patterson (Brian Bothner Lab) 3 pm Byker
Professor Samir Zard from École Polytechnique, Paris will present a seminar in the Byker Auditorium at 3:10 pm. Prof. Matt Cook is the host
Fourth Year Graduate Student Emily Reeves (Sharon Neufeldt Lab) will present "New Methodologies for Selective Palladium-Catalyzed Cross-Coupling Reactions." 3 pm in the Byker Auditorium.
Elizabeth McDaniel, a 4th year graduate student in Prof. Joan Broderick's Lab will present a seminar titled "Discovery of Key Intermediates for Radical SAM Initiation in PFL-AE." 3 pm in the Byker Auditorium
Prof. Hirotomo Nishihara (Tohoku University)
Prof. Jeremy Johnson from the Dept. of Chemistry and BIochemistry at Brigham Young University, will present "Distinguishing Nonlinear Terahertz Excitation Pathways with 2-Dimensional Spectroscopy." Byker Auditorium 3:10 pm. Prof. Erik Grumstrup host.
Dr. David Zigler Assistant Professor from the Dept. of Chemistry and Biochemistry California Polytechnic State University-San Luis Obispo. will present "Electronic State Tuning through Metal-Ligand Covalency: First Row Transition Metals are Worth Exciting!" Byker Auditorium at 3:10 pm. Professor Erik Grumstrup is the host.
Dr. Keith Hollis from the Dept. of Chemistry at Mississippi State University will present "Designing, Developing and Applying Molecules to Solve Tomorrow's Problems: CCC-NHC Pincer Complexes: Early and Late Transition Metal Complexes – Synthesis & Applications." Byker Auditorium at 3:10 pm
Friday, Feb 1-
Dr. Anja Kunze Asst. Professor, Dept. of Electrical and Computer Engineering (MSU) will present "Nano-Scaled Forces for Neurotherapeutics." Byker Auditorium at 3:10 pm
Friday, Feb 8
Prof. Scott Warren from UNC, Chapel Hill will present "2D Heterostructures for Energy Storage and Electronics: Exploring the Limits of Weak and Strong Interlayer Interactions." Byker Auditorium at 3:10 pm. Prof. Nicholas Stadie host.
Dr. Bryan Eichhorn from the University of Maryland, Dept of Chemistry and Biochemistry, will present "Unravelling the Solid-Electrolyte-Interphase (SEI) Chemistry in Li-ion and Li-S Batteries." Byker Auditorium 3:10 pm. Prof. Rob Walker host.
Dr. Mitch Smith (Michigan State, Department of Chemistry) will present "Catalytic C–H and N–H Bond Scission in Fine Chemical Synthesis and Energy Conversion." Byker Auditorium at 3:10 pm. Prof. Joan Broderick is the host.
Dr. Alex Guo (Carnegie Mellon University) will present "Spectroscopic and Kinetic Studies of Catalytically Versatile Non-Heme Iron Enzymes." Byker Auditorium at 3:10 pm. Prof. Jen DuBois host.
Dr. Orion Berryman (University of Montana, Missoula) will present "Anion Triple Helicates: Self-Assembly Directed by Halogen Bonding." Byker Auditorium at 3:10 pm. Professor Mary Cloninger host.
Abstract; Anion directed self-assembly is inherently challenging in part due to the diffuse nature of anions and their variable binding geometries. In particular, the self-assembly of higher order anion helicates in solution is extremely rare. However, halogen bonding offers unique opportunities to address these challenges.
Mr. Eric Smoll will defend his PhD in Chemistry beginning with a seminar titled "Reactive-Atom Scattering Dynamics and Liquid-Vacuum Interfacial Structure." Eric works in the group of Prof. Tim Minton. 2pm ABB 138
Graduate Student Seminar - Max Koch will present "Development of a Multi-omics Method for the Analysis of Alzheimer's Disease. Max works in the lab of Professor Ed Dratz. 1:00 pm in the Byker
Ms. Mackenzie Fricke will defend her PhD in Biochemistry beginning with a seminar titled "Cancer Process Probed by Multivalency: Investigations with Galectin-3 and Lactose Functionalized Dendrimers." 10 am ABB 138. Mackenzie works in the lab of Prof. Mary Cloninger.
Dr. Elliott Hulley (University of Wyoming) will present "Application of FLP Design Strategies to Organometallic Transformations."
Abstract: Metal-carbon bond formation is one of the most important steps in organometallic catalysis, particularly when formed by C-H activation. Understanding the free-energy landscapes of chemical transformations is critical for catalyst design and improvement. Our laboratory has been investigating the thermodynamics of C-H heterolysis, operative in many catalytic C-H functionalizations, using tunable pairs of electrophilic metal complexes and basic proton acceptors (analogous to main group Frustrated Lewis Pairs, FLPs). Advantageous use of FLP-inspired transition metal frameworks requires balancing nucleophile/substrate interactions against the nucleophile/metal interactions that quench metal reactivity and block binding sites. In this talk, recent developments in understanding how C-H bond acidities change upon metal coordination will be discussed, particularly within the context of catalytic organic transformations.
Prof. Michael Mock host
Mr. Luke Berry will defend his PhD in Biochemistry beginning with a seminar titled "Relating Protein Structure to Function: How Protein Dynamics Maximizes Energy Gained by Electron Transfer in an Anaerobic Energy Conservation Mechanism." 11 am in the Byker Auditorium. Luke works in the lab of Professor Brian Bothner.
Jacob Remington will defend his Ph.D. in Chemistry beginning with a seminar titled "Fluorescence Quenching in 2-Aminopurine-Labeled Model DNA Systems." Jacob works in the lab of Regents Professor, Patrik Callis. 11 am Byker
Prof. Timothy Warren (Georgetown University) will present "Modeling Nitric Oxide Signaling Chemistry at Copper and Lewis Acid Sites." 3:10 pm Byker Auditorium. Prof. Warren is the guest of Prof. Michael Mock host
Abstract: Nitric oxide (NO) plays numerous, disparate biological roles that include vasodilation in the cardiovascular system and host defense against microbial pathogens. Nonetheless, the discrete molecular mechanisms involved in NO signaling are not well understood: its molecular relatives S-nitrosothiols (RSNOs) and nitrite (NO2-) can also serve as reservoirs of NO-like behavior. Thus, an understanding of the discrete mechanistic pathways by which these species form, interconvert, and react with molecular targets of biological relevance is crucial to connect nitric oxide to physiological response. Through the use of synthetic models examined in our lab, we share new insights into the interconversion and biological reactivity of key molecules involved in nitric oxide signaling.
Dr. John Kiely will be giving a seminar entitled "An Introduction to Medicinal Chemistry…..More Stuff Than You Ever Wanted to Know." 4:10 pm in the Byker.
Dr. Kiely received his undergraduate degree from Montana State and his Ph.D. from North Dakota State University. He then had a long and productive career in industry working as a medicinal chemist.
Mr. Michael Giroux will defend his M.S in Chemistry beginning with a seminar titled "Effect of Aryldimethylphosphine Electronics on Rate of Oxidative Addition of Aryl Electrophiles at Ni0". 11 am in the Byker Auditorium. Mike works in the lab of Prof. Sharon Neufeldt.
Mr. Samuel Bernhard will present "Glycopolymers as Multivalent Probes of Galectin-3" as part of his PhD defense in Chemistry. Sam works in the lab of Professor Mary Cloninger. 3:10 pm in the Byker Auditorium.
Dr. Jon Tunge from the Department of Chemistry at the University of Kansas will present "Development of Decarboxylative Coupling Reactions." Prof. Matt Cook host
Friday, April 19- University Holiday
Ms. Genevieve Coe will defend her M.S in Biochemistry beginning with a seminar title "The Influence of Iron Bioavailability on the Mammalian Gut Microbiome." Genevieve works in the lab of Prof. Jen DuBois. 1 pm Byker Auditorium.
Ms. Casey Kennedy a fourth year graduate student working in the lab of Professor Erik Grumstrup will present "Carrier Transport and Recombination in Next Generation Photovoltaics." 1 pm in the Byker Auditorium.
Dr. Joan Selverstone Valentine from the Department of Chemistry and Biochemistry, UCLA & Division of Geological & Planetary Sciences, Caltech will present"How Manganese Empowered Life with Dioxygen (and vice versa)."
Throughout the history of life on Earth, abiotic components of the environment have shaped the evolution of life, and life, in turn, has shaped the environment. The element manganese embodies a special aspect of this collaboration; its history is closely entwined with those of photosynthesis and dioxygen —two reigning features that characterize the biosphere today. Manganese chemistry was central to the environmental context and evolutionary innovations that enabled the origin of oxygenic photosynthesis and the ensuing rise of dioxygen. It was also manganese chemistry that provided an early, fortuitous antioxidant system that was instrumental in how life came to cope with oxidative stress and ultimately thrive in an aerobic world. Subsequently, the presence of dioxygen transformed the biogeochemical dynamics of the manganese cycle, enabling a rich suite of environmental and biological processes involving high-valent manganese and manganese redox cycling. Bioinorganic chemistry and geobiology combined help us to understand manganese dynamics in the environment and the unique role of manganese in the history of life.
Graduate students host.
Ms. Katie Link will defend her Ph.D in Chemistry beginning with a seminar titled "Organic Enrichment at Aqueous Interfaces Studied with Non-linear Spectroscopy: Cooperative Adsorption of Soluble Saccharides to Lipid Monolayers." Byker Aditorium at 2:30 pm. Katie works in the lab of Prof. Rob Walker.
Dr. Joe Topczewski (University of Minnesota). Prof. Matt Cook host.
Dr. Matthew Kieber-Emmons from the Department of Chemistry at the University of Utah will present a seminar titled "Mechanistic Insight into Water Oxidation with Copper." Byker Auditorium at 3:10 pm. Prof. Mike Mock is the host.
Friday, Sept 7
Dr. Sean Roberts from the Department of Chemistry at the University of Texas -Austin will be here. Professors Walker and Grumstrup are the hosts.
Monday, Sept 10
Ms. Amanda Byer will defend her Ph.D in Biochemistry beginning with a presentation titled "Radical Chemistry - Mechanism and Function in the Radical SAM Superfamily." Amanda's advisor is Prof. Joan Broderick. 1 pm in the Byker Auditorium.
Friday, Sept 21
Dr. Gerhard Koenig, Research Associate, Institute for Quantitative Biomedicine, Rutgers University will present "Quantitative predictions of chemical equilibria based on computer simulations". Byker Auditorium at 3:10 pm. Prof. Roland Hatzenpichler host.
Friday, Sept 28 -
Dr. Francisco Asturias, from the School of Medicine, Biochemistry and Molecular Genetics, University of Colorado will present "Cryo-EM Studies of Transcriptional Regulation by Mediator." Byker Auditorium at 3:10 pm. Prof. Martin Lawrence host.
Friday, Oct 5- open
Friday, Oct 12
Dr. Tom Autrey, Staff Scientist at PNNL will present "Using calorimetry to understand heterogeneous and homogeneous reactions." Byker Auditorium at 3:10 pm. Prof. Nicholas Stadie is the host.
Abstract: Calorimetry is generally recognized as an experimental technique to obtain thermodynamic data for chemical reactions, however, time dependent measurements of the heat flow can provide additional insight into kinetics of chemical transformation. Our research has ranged from measuring the kinetics and thermodynamics of reactions of reactive intermediates on a microsecond time scale to reactions that occur over days. I look forward to sharing how we use time-resolved reaction calorimetry to gain insight into both heterogeneous and homogeneous catalytic transformations on compounds and materials that show promise for energy storage applications.
Dr. Samuel Gellman from the Dept. of Chemistry at the Univeristy of Wisconsin-Madison will present be "Functional Foldamers." Prof. Mary Cloninger is the host. Byker Auditorium at 3:10 pm. This seminar is sponsored by the Grieco Distinguished Lectureship Series.
Monday, Oct 22
Ph.D. Defense from Greg Prussia. The title of his seminar is "Delineating the determinants of carboxylation in 2-ketopropyl coenzyme M oxidoreductase/carboxylase: A unique CO2-fixing flavoenzyme." 9 am Byker. Greg is advised by Prof. John Peters.
Dr. John Kozarich. Byker Auditorium at 3:10 pm. Prof. Joan Broderick is the host.
Interview with Jon Kozarich
Friday, Nov 2
Kevin Hammonds, Assistant Professor in Civil Engeineering at MSU will present "From Avalanches to Ice Sheets: The Material Properties of Snow & Ice." Byker Auditorium at 3:10 pm.
When studied from a materials science perspective, large-scale and naturally-occurring phenomena, such as how an ice sheet viscously deforms or how an avalanche releases, can be understood through laboratory-scale investigations of the thermal and mechanical history of the snow and/or ice and its microstructure. To derive these microstructural properties, many advanced materials characterization techniques can be employed, including the use of cross-polarized optical microscopy, micro-CT, scanning electron microscopy (including EBSD & EDS), and Raman spectroscopy. With the application of these techniques combined with relatively small-scale laboratory experiments, many of the peculiar properties of ice and snow can begin to be unraveled. Presented in this seminar, is an overview of the materials characterization techniques that are currently being applied to snow and ice at MSU, as well as the results from several previous and ongoing laboratory experiments that will further illustrate its many fascinating complexities. These experiments will include results related to the crystallographic structure of ice, the effects of soluble impurities in ice, and the thermophysical properties of ice/snow interfaces…all of which are critical components for better understanding ice sheets and avalanches in our natural world.
Monday, Nov 5
Ms. Melodie Machovina will defend her Ph.D in Biochemistry beginning with a presentation titled "Enzymatic strategies for harnessing and controlling the oxidative power of O2." Melodie's research advisor is Prof. Jen DuBois, ABB 138 at 3 pm.
Dr. Robert Smith from University of Montana, Dept. of Computing. Byker Auditorium at 3:10 pm. Prof. Brian Bothner host.
Prof. Cecily Ryan (MSU M&IE) will present a seminar titled "Tailoring the mechanical and electrical properties of biopolymer blends via the incorporation of carbon nanofillers."
Biobased fillers, such as bio-derived cellulose, lignin byproducts, and biochar, can be used to modify the thermal, mechanical, and electrical properties of polymer composites. We are interested in using char from lignin and agricultural byproducts to enhance the thermal and electrical conductivities in biopolymer composites. Biochar processed from these feedstocks can potentially serve as a bioderived graphitic carbon alternative for certain composite applications. In this work, we investigate a blended biopolymer system, polyhydroxybutyrate-co-hydroxyvalerate (PHBV) with polylactide (PLA), to control the partitioning of electrically conductive nanofiller, carbon black (CB) and biochar. CB, a commonly used petroleum-derived functional nanofiller, serves as a comparison for our work on the incorporation of biochar into composites. Kraft lignin is the feedstock for the biochar. Particulate affinity for the polymer phases affects nanofiller dispersion. I will present surface energy calculations and experimental results for phase-separation and nanofiller phase affinity in this system and how that modifies the percolation behavior in a phase-separated system. I will also show our initial results for electrical conductivity and mechanical behavior of the mixed-phase nanofilled composites.
Monday, Nov 19
Ms. Danica Walsh (Livinghouse lab) will present her 4th year graduate student research seminar in the Byker Auditorium at 11 am. The title of her presentation is "Design, Synthesis and Evaluation of Prodrugs to Control Biofilms."
Dr. Ohyun Kwon from UCLA. Byker Auditorium at 3:10 pm. Prof. Sharon Neufeldt host.
Title: Phosphine Organocatalysis
Soft nucleophilic phosphinocatalysis has been known since the 1960s as a result of the pioneering work of Horner, Price, Rauhut−Currier, and Morita. In the 1990s, Trost and Lu made important discoveries, reporting isomerization, umpolung addition, and [3+2] cycloaddition. Nonetheless, it was not until the 2000s that the area of phosphinocatalysis began to flourish. My group, through careful analysis of the mechanism of the phosphinocatalysis reactions, has demonstrated over two dozen new reactions facilitated by phosphine catalysts. The results are a one-step conversion of simple acyclic starting materials into various carbo- and heterocycles. The practical values of these one-step phosphine-catalyzed annulation processes are significant since (1) they are atom economic and environmentally friendly, and (2) the heterocycles are an immense class of organic compounds with numerous practical applications. One recent, particularly significant advancement is the creation of chiral phosphines that are derived from a natural amino acid, L-hydroxyproline. Their synthetic utility in the phosphine catalyzed annulations, application in total syntheses of (+)-ibophyllidine and (–)-actinophyllic acid, and commercialization will also be discussed. The phosphinocatalysis reactions that my group has developed have produced structurally varied heterocycles of immense value for numerous practical applications. To illustrate the utility of these heterocycles, my group has been engaged in chemical genetic studies, resulting in the identification of the following bio-modulators: (1) inhibitors of the enzymes GGTase‐I and Rab GGTase; (2) an anti-arrhythmic agent (named "efsevin") to rescue zebrafish tremblor mutant; (3) an inhibitor (named "aplexone") of cholesterol biosynthesis that is more potent than Pfizer's Lipitor; (4) compounds inhibiting cell migration and cell invasion; (5) interferon γ‐like compounds that augment innate immune responses of macrophages; (6) inhibitors of cytotoxic T cell lytic granule exocytosis; and (7) inhibitors of serine hydrolases that are specific for platelet-activating factor acetylhydrolases 1b2 and 1b3 (PAFAH1b2/3). Chemical biological studies related with these molecules will be presented during the talk. In addition, recent development in phosphine oxide catalysis research will also be introduced.
Wedneday, Dec 5
Ms. Elizabeth Corbin will defend her Ph.D. in Biochemistry beginning with a seminar titled "Complexation of Lipids with Cyclodextrin Carriers for Fully Defined Supplementation of Cell Culture." 2 pm in the Byker Auditorium. Elizabeth works in the laboratory of Professor Ed Dratz.
Capstone senior seminars for the Department of Chemistry and Biochemistry will be presented from 1-3 pm in the first floor conference room in the Chemistry and Biochemistry Building. Presenters are Tricia Brandenburg, Daniel Goettlich, Matt Hall, Alex Morren and Alexia Olson.
Titles of Presentations
Alexia Olson "Agrobacterium tumefaciens/arsenic" Advisor: Valerie Copié
Daniel Goettlich "In situ, high temperature characterization of proton conducting ceramics using Raman spectroscopy" Advisor: Rob Walker
Tricia Brandenburg "Polyurethane Chemistry and working in industry" Advisor: Alan Cain, Chemline
Matt Hall "Computationally Generated Ionic Liquids." Advisor: Tim Minton
Dr. Sergey Pronin from the Department of Chemistry at UC Irvine will present "New methods and Strategies in the Synthesis of Natural Products." 3:10 pm in the Byker. Prof. Tom Livinghouse host.
Mr. Chase Austvold will defend his MS in Biochemistry beginning with a seminar titled "Partitioning of Reactive Oxygen Species via the Re-Oxidation of Electron Transfer Flavoprotein." Chase is advised by Prof. Ed Dratz.
Thursday, Dec 13
Fourth year Graduate Student Seminar
Ms. Ece Topuzlu, Department Chemistry & Biochemistry, Montana State University
Title: Biophysical and Surface Characterization of Plastic Degrading Polyesterases
Abstract: Recalcitrance to natural degradation of synthetic plastics such as poly(ethylene terephthalate) (PET) is problematic in the world's ecosystems. Several cutinases isolated from fungal species have been shown to enzymatically degrade PET to a limited extent. The discovery of Ideonella sakaiensis, and its ability to grow on PET as a major carbon source has led to the identification of two of the key enzymes responsible for hydrolysis of PET. These enzymes, named PETase and MHETase, act in a concerted manner to convert PET into its monomers and building blocks, respectively. This seminar will highlight the enzymatic capabilities of PETase on industrially relevant substrates, its localization in cells in vivo, and its synergistic activity with MHETase for PET degradation.
12 noon in the Byker. Ece is in the lab of Professor Valérie Copié
103 Chemistry and Biochemistry Building
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