Studies on the Hemoglobin of Cooley's Anemia and Cooley's Trait

The diseases sickle cell anemia and Cooley's anemia (also known as thalassemia or Mediterranean anemia) have associated with them "minor" or "trait" forms of the disease in which the symptomatology is minimal, and the abnormalities in the red cells are correspondingly less. Extensive genetic studies carried out on these diseases [1-4] have led to the conclusion that in each case the trait is inherited as a Mendalian dominant, the person being heterozygous in the sickle cell gene or Cooley's gene. Homozygosity in either of these genes leads to the corresponding anemia. Our understanding of sickle cell anemia has improved considerably with the discovery of an abnormal hemoglobin and a molecular interpretation of the pathological behavior of the red cell. [5] In that disease it was possible to demonstrate heterozygosity and homozygosity directly, by observing varying amounts of the abnormal hemoglobin. Liquori [6] has recently reported the pr'esence of fetal hemoglobin in cases of Cooley's anemia. We have carried out a number of experiments which support his findings, and have extended the investigation to include cases of Cooley's trait, for which no fetal hemoglobin was found. A hypothesis is advanced to explain these facts

Different forms of the double helix: architecture and function

The DNA double helix was discovered 50 years ago. This motif was found in several other places, most notably in RNA molecules. It is also found in DNA-RNA hybrids as well as transfer RNA molecules where double helical segments combine to form a more complex structure. A distinct variant of the DNA molecule was discovered in which the helix turns left-handed, which has led to practical consequences in the treatment of certain viral diseases. Since the molecule readily converted from A to B form, it clearly suggested that there was another form the double helix could adopt in the A form. Thus, the initial mystery ?why are there two such forms? It was known at the time that there are two major nucleic acids, one DNA and the other RNA, in which the sugar phosphate backbone contained ribose rather than the deoxyribose of DNA. One of the early questions that arose immediately after the Watson-Crick formulation was related to the nature of the RNA molecule-could it form a double helix

Corey Rich

This project initially started out as a collection of found wood pieces, which I then sorted, sanded, and painted. I took some parts from recycling bins at Fisher and UBS as well as finding some random chunks at my house. Other wood was either collected in similar ways except for 3 2x4’s which I purchased. Through the process of mixing and matching the color and shape of each wooden chunk I found it easier for each piece to find its place among the rest. Like a puzzle for me to find the correct spot for the item at hand. It wasn’t until I had made a few of these bright pieces with individually painted parts that I came to the realization that I was trying to fix something that had already been broken once before (by myself or another). Through this understanding, I started breaking the wood up myself. I believe this trial of material mash helped me think about the wood differently than I had before and seriously try to make this 2x4 mine. Trying out more combinations with less vocal colors. Once I started using textiles throughout the first semester I started to pick up on the fact that I was likely making my work as some sort of memorial and connecting with feelings of nostalgia both positive and negative from my childhood. I make these pieces with the idea of a “family” in mind. The pieces belong to one another, or one is related to another but not the rest. I want to fix the broken family and in order to figure out how it works it must be destroyed and put back together. Not just by breaking, but pounding, destroying, obliterating, until what was left could only be understood as wood. And once this wood is unfamiliar, mend it back together with the tools at hand. S, P, C Snapping, playing and crunching Like feet stomping in the forest Chirping children Tattered twigs Scraping, prying and clipping Like opening a gift From surprise To shock Salvaging, patching and crafting Like a Surgeon From static To stagnant Splitting, popping and cracking Like bones From the Earth Back to the dirt Sanding, polishing and cleaning Like Morticians From the bed Into the coffin Saving, protecting and cubbying Like a mourning Mother From disbelief To grief Smothering, priming and coating Like a role model Gone now Never forgotten Spraying, pigmenting and coloring Like flowers From vibrant bloom To Winter’s grey Searching, prowling and collecting Like a hungry animal Once stuffed Now empty Stoning, plummeting and cascading Like a landslide Head under a boulder And it feels real Sleeping, psychoanalyzing and cuddling Like a velvet couch The ceilings are always grey And they’re never comfortable Sparking, pitter-pattering and catching Like a fuse Tik-tik Boom Speeding, producing and cruising Like a machine Gears squeaky Gunky stuck Slipping, parading and crashing Like a drunk All smiles at day Cries at night Salting, powdering and crusting Like a grill master Mouthwatering sweet With a fiery kick Splintering, pulling and creaking Like a heavy wind Trees falling down Precious wood In the ground is a birch tree Planted along with half of me

Uncovering and Mitigating Algorithmic Bias through Learned Latent Structure

Recent research has highlighted the vulnerabilities of modern machine learning based systems to bias, especially for segments of society that are under-represented in training data. In this work, we develop a novel, tunable algorithm for mitigating the hidden, and potentially unknown, biases within training data. Our algorithm fuses the original learning task with a variational autoencoder to learn the latent structure within the dataset and then adaptively uses the learned latent distributions to re-weight the importance of certain data points while training. While our method is generalizable across various data modalities and learning tasks, in this work we use our algorithm to address the issue of racial and gender bias in facial detection systems. We evaluate our algorithm on the Pilot Parliaments Benchmark (PPB), a dataset specifically designed to evaluate biases in computer vision systems, and demonstrate increased overall performance as well as decreased categorical bias with our debiasing approach

A 6 bp Z-DNA hairpin binds two Zα domains from the human RNA editing enzyme ADAR1

AbstractThe Zα domain of the human RNA editing enzyme double-stranded RNA deaminase I (ADAR1) binds to left-handed Z-DNA with high affinity. We found by analytical ultracentrifugation and CD spectroscopy that two Zα domains bind to one d(CG)3T4(CG)3 hairpin which contains a stem of six base pairs in the Z-DNA conformation. Both wild-type Zα and a C125S mutant show a mean dissociation constant of 30 nM as measured by surface plasmon resonance and analytical ultracentrifugation. Our data suggest that short (≥6 bp) segments of Z-DNA within a gene are able to recruit two ADAR1 enzymes to that particular site

Nucleozymes

Nucleozymes containing ribonucleotides and deoxyribonucleotides or nucleic acid analogues are described herein. The nucleozymes have catalytic activity and are significantly more resistant to degradation than their all-RNA ribozyme counterparts. Also described are methods for preparing the nucleozymes along with methods of using nucleozymes, e.g., as therapeutic agents

Induction chemotherapy in the treatment of nasopharyngeal carcinoma: Clinical outcomes and patterns of care

Abstract The role of induction chemotherapy in nasopharyngeal carcinoma (NPC) remains controversial. The primary aim of this study was to use the National Cancer Database to evaluate the patterns of care of induction chemotherapy in NPC and its impact on overall survival (OS). Patients with NPC from 2004 to 2014 were obtained from the NCDB. Patients were considered to have received induction chemotherapy if it was started ≥43 days before the start of RT and concurrent CRT if chemotherapy started within 21 days after the start of RT. Propensity score matching was used to control for selection bias. Cox proportional hazards model was used to determine significant predictors of OS. Logistic regression model was used to determine predictors of the use of induction chemotherapy. Significance was defined as a P value <.05. A total of 4857 patients were identified: 4041 patients (87.2%) received concurrent CRT and 816 patients (16.8%) received induction chemotherapy. The use of induction therapy remained stable between 2004 and 2014. Younger patients and those with higher T‐ and N‐stage had a higher likelihood of being treated with induction chemotherapy. The 5‐year OS in patients treated with induction chemotherapy and CRT was 66.3% vs 69.1%, respectively (P = .25). There was no difference in OS when these two groups were analyzed after propensity score matching. No differences in OS existed between these treatment groups in patients with T3‐T4N1 or TanyN2‐3 disease (P = .76). Propensity score matching also did not reveal any difference in OS in patients with T3‐T4N1 or TanyN2‐3 disease. The use of induction chemotherapy has remained stable in the last decade. In this study of patients with NPC, induction chemotherapy was not associated with improved OS compared to CRT alone

Nonsteroidal Anti-Inflammatory Agents in the Therapy for Experimental Pneumococcal Meningitis

An increased inflammatory mass in the subarachnoid space during bacterial meningitis may correlate with a poor outcome of disease. Using a rabbit model of pneumococcal meningitis, we sought to reduce this inflammatory process. The ability of the pneumococcal cell wall to cause death and to generate leukocytosis and abnormal chemistry in cerebrospinal fluid was prevented when animals were treated with inhibitors of the cyclooxygenase pathway of arachidonate metabolism. Bacterial lysis by ampicillin led to release of cell wall that caused a significant, transient increase in meningeal inflammation. This inflammatory burst was also prevented by administering cyclooxygenase inhib-itors concurrently with the antibioti

The Attentional Learning Trap and How to Avoid It

People often make repeated decisions from experience. In such scenarios, persistent biases of choice can develop, most notably the “hot stove effect” (Denrell &amp; March, 2001) in which a prospect that is mistakenly believed to be negative is avoided and thus belief-correcting information is never obtained. In the existing literature, the hot stove effect is generally thought of as developing through interaction with a single, stochastic prospect. Here, we show how a similar bias can develop due to people’s tendency to selectively attend to a subset of features during categorization. We first explore the bias through model simulation, then report on an experiment in which we find evidence of a decisional bias linked to selective attention. Finally, we use these computational models to design novel interventions to “de-bias” decision-makers, some of which may have practical applicatio

Characterization of DNA-binding activity of Zα domains from poxviruses and the importance of the β-wing regions in converting B-DNA to Z-DNA

The E3L gene is essential for pathogenesis in vaccinia virus. The E3L gene product consists of an N-terminal Zα domain and a C-terminal double-stranded RNA (dsRNA) binding domain; the left-handed Z-DNA-binding activity of the Zα domain of E3L is required for viral pathogenicity in mice. E3L is highly conserved among poxviruses, including the smallpox virus, and it is likely that the orthologous Zα domains play similar roles. To better understand the biological function of E3L proteins, we have investigated the Z-DNA-binding behavior of five representative Zα domains from poxviruses. Using surface plasmon resonance (SPR), we have demonstrated that these viral Zα domains bind Z-DNA tightly. Ability of Zα[subscript E3L] converting B-DNA to Z-DNA was measured by circular dichroism (CD). The extents to which these Zαs can stabilize Z-DNA vary considerably. Mutational studies demonstrate that residues in the loop of the β-wing play an important role in this stabilization. Notably the Zα domain of vaccinia E3L acquires ability to convert B-DNA to Z-DNA by mutating amino acid residues in this region. Differences in the host cells of the various poxviruses may require different abilities to stabilize Z-DNA; this may be reflected in the observed differences in behavior in these Zα proteins.Korean Science and Engineering Foundation (National Research Laboratory Program (NRL-2006-02287))Korean Science and Engineering Foundation (Ubiquitome Research Program (M10533010002-06N3301-00210))Korean Science and Engineering Foundation (21C Frontier Functional Proteomics Program (FPR06B2-120))National Institutes of Health (U.S.)Ellison Medical FoundationKorea (South). Ministry of Science and Technology (National Laboratory program (NRL-2006-02287)