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The Tybo Charcoal Kilns are a pair of charcoal kilns located 4 miles (6.4 km) north of Tybo, Nevada. Both kilns are 30 feet (9.1 m) tall and 25 feet (7.6 m) in diameter and were built from rocks and mud. The kilns each have three openings: a top opening, a door at ground level, and a rear window with a ramp for wood wagons. The kilns were among 15 built in 1874 for the Tybo Consolidated Company. The company, which mined the region's silver, used charcoal to fuel its smelting furnace. To acquire its fuel, it imported wood from nearby hills, which it then converted to charcoal in the kilns. The kilns were built during a mining boom in the area around Tybo. Though the community had only been settled in 1870, by the end of the decade it had a post office, school, newspaper, and almost 1000 residents. The kilns were added to the National Register of Historic Places on November 19, 1974. == References == == External links == Photos from the NRHP nomination
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"title": "Tybo Charcoal Kilns"
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Maximal entropy random walk (MERW) is a popular type of biased random walk on a graph, in which transition probabilities are chosen accordingly to the principle of maximum entropy, which says that the probability distribution which best represents the current state of knowledge is the one with largest entropy. While standard random walk chooses for every vertex uniform probability distribution among its outgoing edges, locally maximizing entropy rate, MERW maximizes it globally (average entropy production) by assuming uniform probability distribution among all paths in a given graph. MERW is used in various fields of science. A direct application is choosing probabilities to maximize transmission rate through a constrained channel, analogously to Fibonacci coding. Its properties also made it useful for example in analysis of complex networks, like link prediction, community detection, robust transport over networks and centrality measures. Also in image analysis, for example for detecting visual saliency regions, object localization, tampering detection or tractography problem. Additionally, it recreates some properties of quantum mechanics, suggesting a way to repair the discrepancy between diffusion models and quantum predictions, like Anderson localization. == Basic model == Consider a graph with n {\displaystyle n} vertices, defined by an adjacency matrix A ∈ { 0 , 1 } n × n {\displaystyle A\in \left\{0,1\right\}^{n\times n}} : A i j = 1 {\displaystyle A_{ij}=1} if there is an edge from vertex i {\displaystyle i} to j {\displaystyle j} , 0 otherwise. For simplicity assume it is an undirected graph, which corresponds to a symmetric A {\displaystyle A} ; however, MERW can also be generalized for directed and weighted graphs (for example Boltzmann distribution among paths instead of uniform). We would like to choose a random walk as a Markov process on this graph: for every vertex i {\displaystyle i} and its outgoing edge to j
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"page_id": 53153455,
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{\displaystyle j} , choose probability S i j {\displaystyle S_{ij}} of the walker randomly using this edge after visiting i {\displaystyle i} . Formally, find a stochastic matrix S {\displaystyle S} (containing the transition probabilities of a Markov chain) such that 0 ≤ S i j ≤ A i j {\displaystyle 0\leq S_{ij}\leq A_{ij}} for all i , j {\displaystyle i,j} and ∑ j = 1 n S i j = 1 {\displaystyle \sum _{j=1}^{n}S_{ij}=1} for all i {\displaystyle i} . Assuming this graph is connected and not periodic, ergodic theory says that evolution of this stochastic process leads to some stationary probability distribution ρ {\displaystyle \rho } such that ρ S = ρ {\displaystyle \rho S=\rho } . Using Shannon entropy for every vertex and averaging over probability of visiting this vertex (to be able to use its entropy), we get the following formula for average entropy production (entropy rate) of the stochastic process: H ( S ) = ∑ i = 1 n ρ i ∑ j = 1 n S i j log ( 1 / S i j ) {\displaystyle H(S)=\sum _{i=1}^{n}\rho _{i}\sum _{j=1}^{n}S_{ij}\log(1/S_{ij})} This definition turns out to be equivalent to the asymptotic average entropy (per length) of the probability distribution in the space of paths for this stochastic process. In the standard random walk, referred to here as generic random walk (GRW), we naturally choose that each outgoing edge is equally probable: S i j = A i j ∑ k = 1 n A i k {\displaystyle S_{ij}={\frac {A_{ij}}{\sum \limits _{k=1}^{n}A_{ik}}}} . For a symmetric A {\displaystyle A} it leads to a stationary probability distribution ρ {\displaystyle \rho } with ρ i = ∑ j = 1 n A i j ∑ i = 1 n ∑ j = 1 n A
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"page_id": 53153455,
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i j {\displaystyle \rho _{i}={\frac {\sum \limits _{j=1}^{n}A_{ij}}{\sum \limits _{i=1}^{n}\sum \limits _{j=1}^{n}A_{ij}}}} . It locally maximizes entropy production (uncertainty) for every vertex, but usually leads to a suboptimal averaged global entropy rate H ( S ) {\displaystyle H(S)} . MERW chooses the stochastic matrix which maximizes H ( S ) {\displaystyle H(S)} , or equivalently assumes uniform probability distribution among all paths in a given graph. Its formula is obtained by first calculating the dominant eigenvalue λ {\displaystyle \lambda } and corresponding eigenvector ψ {\displaystyle \psi } of the adjacency matrix, i.e. the largest λ ∈ R {\displaystyle \lambda \in \mathbb {R} } with corresponding ψ ∈ R n {\displaystyle \psi \in \mathbb {R} ^{n}} such that ψ A = λ ψ {\displaystyle \psi A=\lambda \psi } . Then stochastic matrix and stationary probability distribution are given by S i j = A i j λ ψ j ψ i {\displaystyle S_{ij}={\frac {A_{ij}}{\lambda }}{\frac {\psi _{j}}{\psi _{i}}}} for which every possible path of length l {\displaystyle l} from the i {\displaystyle i} -th to j {\displaystyle j} -th vertex has probability 1 λ l ψ j ψ i {\displaystyle {\frac {1}{\lambda ^{l}}}{\frac {\psi _{j}}{\psi _{i}}}} . Its entropy rate is log ( λ ) {\displaystyle \log(\lambda )} and the stationary probability distribution ρ {\displaystyle \rho } is ρ i = ψ i 2 ‖ ψ ‖ 2 2 {\displaystyle \rho _{i}={\frac {\psi _{i}^{2}}{\|\psi \|_{2}^{2}}}} . In contrast to GRW, the MERW transition probabilities generally depend on the structure of the entire graph (are nonlocal). Hence, they should not be imagined as directly applied by the walker – if random-looking decisions are made based on the local situation, like a person would make, the GRW approach is more appropriate. MERW is based on the principle of maximum entropy, making it
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"page_id": 53153455,
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the safest assumption when we don't have any additional knowledge about the system. For example, it would be appropriate for modelling our knowledge about an object performing some complex dynamics – not necessarily random, like a particle. === Sketch of derivation === Assume for simplicity that the considered graph is indirected, connected and aperiodic, allowing to conclude from the Perron–Frobenius theorem that the dominant eigenvector is unique. Hence A l {\displaystyle A^{l}} can be asymptotically ( l → ∞ {\displaystyle l\rightarrow \infty } ) approximated by λ l ψ ψ T {\displaystyle \lambda ^{l}\psi \psi ^{T}} (or λ l | ψ ⟩ ⟨ ψ | {\displaystyle \lambda ^{l}|\psi \rangle \langle \psi |} in bra–ket notation). MERW requires uniform distribution along paths. The number m i l {\displaystyle m_{il}} of paths with length 2 l {\displaystyle 2l} and vertex i {\displaystyle i} in the center is m i l = ∑ j = 1 n ∑ k = 1 n ( A l ) j i ( A l ) i k ≈ ∑ j = 1 n ∑ k = 1 n ( λ l ψ ψ ⊤ ) j i ( λ l ψ ψ ⊤ ) i k = ∑ j = 1 n ∑ k = 1 n λ 2 l ψ j ψ i ψ i ψ k = λ 2 l ψ i 2 ∑ j = 1 n ψ j ∑ k = 1 n ψ k ⏟ =: b {\displaystyle m_{il}=\sum _{j=1}^{n}\sum _{k=1}^{n}\left(A^{l}\right)_{ji}\left(A^{l}\right)_{ik}\approx \sum _{j=1}^{n}\sum _{k=1}^{n}\left(\lambda ^{l}\psi \psi ^{\top }\right)_{ji}\left(\lambda ^{l}\psi \psi ^{\top }\right)_{ik}=\sum _{j=1}^{n}\sum _{k=1}^{n}\lambda ^{2l}\psi _{j}\psi _{i}\psi _{i}\psi _{k}=\lambda ^{2l}\psi _{i}^{2}\underbrace {\sum _{j=1}^{n}\psi _{j}\sum _{k=1}^{n}\psi _{k}} _{=:b}} , hence for all i {\displaystyle i} , ρ i = lim l → ∞ m i l ∑ k = 1 n m
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"page_id": 53153455,
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k l = lim l → ∞ λ 2 l ψ i 2 b ∑ k = 1 n λ 2 l ψ k 2 b = lim l → ∞ ψ i 2 ∑ k = 1 n ψ k 2 = ψ i 2 ∑ k = 1 n ψ k 2 = ψ i 2 ‖ ψ ‖ 2 2 {\displaystyle \rho _{i}=\lim _{l\rightarrow \infty }{\frac {m_{il}}{\sum \limits _{k=1}^{n}m_{kl}}}=\lim _{l\rightarrow \infty }{\frac {\lambda ^{2l}\psi _{i}^{2}b}{\sum \limits _{k=1}^{n}\lambda ^{2l}\psi _{k}^{2}b}}=\lim _{l\rightarrow \infty }{\frac {\psi _{i}^{2}}{\sum \limits _{k=1}^{n}\psi _{k}^{2}}}={\frac {\psi _{i}^{2}}{\sum \limits _{k=1}^{n}\psi _{k}^{2}}}={\frac {\psi _{i}^{2}}{\|\psi \|_{2}^{2}}}} . Analogously calculating probability distribution for two succeeding vertices, one obtains that the probability of being at the i {\displaystyle i} -th vertex and next at the j {\displaystyle j} -th vertex is ψ i A i j ψ j ∑ i ′ = 1 n ∑ j ′ = 1 n ψ i ′ A i ′ j ′ ψ j ′ = ψ i A i j ψ j ψ A ψ ⊤ = ψ i A i j ψ j λ ‖ ψ ‖ 2 2 {\displaystyle {\frac {\psi _{i}A_{ij}\psi _{j}}{\sum \limits _{i'=1}^{n}\sum \limits _{j'=1}^{n}\psi _{i'}A_{i'j'}\psi _{j'}}}={\frac {\psi _{i}A_{ij}\psi _{j}}{\psi A\psi ^{\top }}}={\frac {\psi _{i}A_{ij}\psi _{j}}{\lambda \|\psi \|_{2}^{2}}}} . Dividing by the probability of being at the i {\displaystyle i} -th vertex, i.e. ρ i {\displaystyle \rho _{i}} , gives for the conditional probability S i j {\displaystyle S_{ij}} of the j {\displaystyle j} -th vertex being next after the i {\displaystyle i} -th vertex S i j = A i j λ ψ j ψ i {\displaystyle S_{ij}={\frac {A_{ij}}{\lambda }}{\frac {\psi _{j}}{\psi _{i}}}} . === Weighted MERW: Boltzmann path ensemble === We have assumed that A i j ∈ { 0 , 1 } {\displaystyle A_{ij}\in \{0,1\}} ,
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"page_id": 53153455,
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yielding a MERW corresponding to the uniform ensemble among paths. However, the above derivation works for any real nonnegative A {\displaystyle A} for which the Perron-Frobenius theorem applies. Given A i j = exp ( − E i j ) {\displaystyle A_{ij}=\exp(-E_{ij})} , the probability of a particular length- l {\displaystyle l} path ( γ 0 , … , γ l ) {\displaystyle (\gamma _{0},\ldots ,\gamma _{l})} is as follows: Pr ( γ 0 , … , γ l ) = ρ γ 0 S γ 0 γ 1 … S γ l − 1 γ l = ψ γ 0 A γ 0 γ 1 … A γ l − 1 γ l λ l ψ γ l = ψ γ 0 exp ( − ( E γ 0 γ 1 + … + E γ l − 1 γ l ) ) λ l ψ γ l {\displaystyle {\textrm {Pr}}(\gamma _{0},\ldots ,\gamma _{l})=\rho _{\gamma _{0}}S_{\gamma _{0}\gamma _{1}}\ldots S_{\gamma _{l-1}\gamma _{l}}=\psi _{\gamma _{0}}{\frac {A_{\gamma _{0}\gamma _{1}}\ldots A_{\gamma _{l-1}\gamma _{l}}}{\lambda ^{l}}}\psi _{\gamma _{l}}=\psi _{\gamma _{0}}{\frac {\exp(-(E_{\gamma _{0}\gamma _{1}}+\ldots +E_{\gamma _{l-1}\gamma _{l}}))}{\lambda ^{l}}}\psi _{\gamma _{l}}} , which is the same as the Boltzmann distribution of paths with energy defined as the sum of E i j {\displaystyle E_{ij}} over the edges of the path. For example, this can be used with the transfer matrix to calculate the probability distribution of patterns in the Ising model. == Examples == Let us first look at a simple nontrivial situation: Fibonacci coding, where we want to transmit a message as a sequence of 0s and 1s, but not using two successive 1s: after a 1 there has to be a 0. To maximize the amount of information transmitted in such sequence, we should assume uniform probability distribution in the space of all
|
{
"page_id": 53153455,
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"title": "Maximal entropy random walk"
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possible sequences fulfilling this constraint. To practically use such long sequences, after 1 we have to use 0, but there remains a freedom of choosing the probability of 0 after 0. Let us denote this probability by q {\displaystyle q} , then entropy coding would allow encoding a message using this chosen probability distribution. The stationary probability distribution of symbols for a given q {\displaystyle q} turns out to be ρ = ( 1 / ( 2 − q ) , 1 − 1 / ( 2 − q ) ) {\displaystyle \rho =(1/(2-q),1-1/(2-q))} . Hence, entropy production is H ( S ) = ρ 0 ( q log ( 1 / q ) + ( 1 − q ) log ( 1 / ( 1 − q ) ) ) {\displaystyle H(S)=\rho _{0}\left(q\log(1/q)+(1-q)\log(1/(1-q))\right)} , which is maximized for q = ( 5 − 1 ) / 2 ≈ 0.618 {\displaystyle q=({\sqrt {5}}-1)/2\approx 0.618} , known as the golden ratio. In contrast, standard random walk would choose suboptimal q = 0.5 {\displaystyle q=0.5} . While choosing larger q {\displaystyle q} reduces the amount of information produced after 0, it also reduces frequency of 1, after which we cannot write any information. A more complex example is the defected one-dimensional cyclic lattice: let say 1000 nodes connected in a ring, for which all nodes but the defects have a self-loop (edge to itself). In standard random walk (GRW) the stationary probability distribution would have defect probability being 2/3 of probability of the non-defect vertices – there is nearly no localization, also analogously for standard diffusion, which is infinitesimal limit of GRW. For MERW we have to first find the dominant eigenvector of the adjacency matrix – maximizing λ {\displaystyle \lambda } in: ( λ ψ ) x = (
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"page_id": 53153455,
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"title": "Maximal entropy random walk"
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A ψ ) x = ψ x − 1 + ( 1 − V x ) ψ x + ψ x + 1 {\displaystyle (\lambda \psi )_{x}=(A\psi )_{x}=\psi _{x-1}+(1-V_{x})\psi _{x}+\psi _{x+1}} for all positions x {\displaystyle x} , where V x = 1 {\displaystyle V_{x}=1} for defects, 0 otherwise. Substituting 3 ψ x {\displaystyle 3\psi _{x}} and multiplying the equation by −1 we get: E ψ x = − ( ψ x − 1 − 2 ψ x + ψ x + 1 ) + V x ψ x {\displaystyle E\psi _{x}=-(\psi _{x-1}-2\psi _{x}+\psi _{x+1})+V_{x}\psi _{x}} where E = 3 − λ {\displaystyle E=3-\lambda } is minimized now, becoming the analog of energy. The formula inside the bracket is discrete Laplace operator, making this equation a discrete analogue of stationary Schrodinger equation. As in quantum mechanics, MERW predicts that the probability distribution should lead exactly to the one of quantum ground state: ρ x ∝ ψ x 2 {\displaystyle \rho _{x}\propto \psi _{x}^{2}} with its strongly localized density (in contrast to standard diffusion). Taking the infinitesimal limit, we can get standard continuous stationary (time-independent) Schrodinger equation ( E ψ = − C ψ x x + V ψ {\displaystyle E\psi =-C\psi _{xx}+V\psi } for C = ℏ 2 / 2 m {\displaystyle C=\hbar ^{2}/2m} ) here. == See also == Principle of maximum entropy Eigenvector centrality Markov chain Anderson localization == References == == External links == Gábor Simonyi, Y. Lin, Z. Zhang, "Mean first-passage time for maximal-entropy random walks in complex networks". Scientific Reports, 2014. Electron Conductance Models Using Maximal Entropy Random Walks Wolfram Demonstration Project
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"page_id": 53153455,
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"title": "Maximal entropy random walk"
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Pinch-induced behavioral inhibition (PIBI), also called dorsal immobility, transport immobility, clipnosis, or scruffing, is a partially inert state that results from a gentle squeeze of the nape, the skin at the back of the neck. It is mostly observed among cats and allows a mother cat to carry her kitten easily with her jaws. It can be used to restrain most cats effectively in a domestic or veterinary context, however it is no longer recommended as studies have shown significant fear-anxiety responses and aversion in cats who have this technique used on them. The phenomenon also occurs in other animals, such as squirrels and mice. == See also == Tonic immobility == References ==
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{
"page_id": 44961465,
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"title": "Pinch-induced behavioral inhibition"
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In physics and chemistry, the Lyman limit is the short-wavelength end of the Lyman series of hydrogen emission lines at 91.13 nm (911.3 Å). The associated photon energy, 13.6 eV, corresponds to the energy required for an electron in the hydrogen ground state to escape from the electric potential barrier that originally confined it, thus creating a hydrogen ion. This energy is equivalent to the Rydberg constant. == See also == Lyman–Werner photons Balmer series Balmer break Lyman-break galaxy Lyman-alpha emitter Lyman-alpha forest == References ==
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{
"page_id": 21761715,
"source": null,
"title": "Lyman limit"
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The molecular formula C22H24N2O8 (molar mass: 444.43 g/mol, exact mass: 444.1533 u) may refer to: Tetracycline Doxycycline
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"page_id": 24710843,
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"title": "C22H24N2O8"
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The Immunologic Constant of Rejection (ICR), is a notion introduced by biologists to group a shared set of genes expressed in tissue destructive-pathogenic conditions like cancer and infection, along a diverse set of physiological circumstances of tissue damage or organ failure, including autoimmune disease or allograft rejection. The identification of shared mechanisms and phenotypes by distinct immune pathologies, marked as a hallmarks or biomarkers, aids in the identification of novel treatment options, without necessarily assessing patients phenomenologies individually. == Concept == The concept of immunologic constant of rejection is based on the proposition that: Tissue-specific destruction does not necessarily only occur after non-self recognition of the body, but can also occur against self- or quasi-self; such as the phenotypes observed in autoimmune diseases. Immune cells required for the induction of a cognate/adaptive immune response differ from those cells necessary for the activation of an effector immune response. Although the causes of tissue-specific destruction vary among pathologic states, the effector immune response observed in these conditions is found to converge into one single mechanism, including the activation of adaptive and innate cytotoxic mechanisms. Adaptive immunity participates as a tissue-specific trigger, but it is not always sufficient or necessary for tissue destruction. Intensive work on factors activated during immune-mediated rejection have concluded that tissue-specific destruction is correlated with the expression of interferons (IFNa and IFNy), and Interferon-stimulated gene (ISGs). == Mechanism == In the case of autoimmunity and/or allograft rejection, immunity broadens in the target organ by producing chemokines of the CXCL family that recruit the receptor CXCR3-bearing cytotoxic T cells. These initiate the following cascade: CXCR3 ligand chemokines (CXCL-9, -10 and -11) are produced in response to activated B cells and the pro-inflammatory secretion of interleukin 12 (IL12) and/or interferon-gamma (IFNy) by antigen-presenting cells (APCs). CXCR3 expressing Th1-polarized CD4 T cells
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"page_id": 52956862,
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and cytotoxic T cells are recruited to the site of acute inflammation. Antigen-activated T cells secrete CCR5 ligands (CCL2 and CCL3) to recruit natural killer (NK) cells and other innate immune effector cells to the site of acute inflammation. Several cytotoxic mechanisms converge on the target tissue, and its complete destruction occurs through the activated effects of CTLs, NK cells, granulocytes, macrophages and dendritic cells. As such, 20 genes involved in this cascade make up the ICR gene set, including: T helper type 1 (Th1) cell-related factors such as IFNy, signal transducers and activator of transcription 1 (STAT1), IL12B, Interferon-regulatory factor 1 (IRF1), the transcription factor T-bet (TBX21). CD8 Tcell markers : CD8A & CD8B Immune effector or cytotoxic factors like the granzymes GZMA, GZMB, GZMH, perforin PRF1, and granulysin GNLY. Chemokine ligands CXCL9, CXCL10, and CCL5 that bind to chemokine receptors such as CXCR3 and CCR5, Immune suppressive or counter regulatory genes like IDO1, PDCD1, PDL1 (CD274), CTLA4 and FOXP3 == Clinical significance == === Cancer === The disrupted homeostasis of cancer cells is found to initiate processes promoting cell growth. To illustrate, growth factors and chemokines activated in response to injury are recruited by tumour cells, sustaining chronic inflammation; similarly to the immune phenotype found in chronic infection, allograft rejection and autoimmunity diseases. The role of immunity in cancer is demonstrated by the predictive and prognostic role of tumour-infiltrating lymphocytes (TIL) and immune response gene signatures. In several cancers these genes show great correlation. A high expression of these genes indicates an active immune engagement, and at least a partial rejection of the cancer tissue. ==== Breast Cancer ==== In breast cancer increased survival is observed in patients displaying a high level of ICR gene expression. This immune active phenotype was associated with an increased level of mutations
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"page_id": 52956862,
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while the poor immune phenotype was defined by perturbation in the MAPK signalling pathways. The consensus clustering of tumours based on ICR gene expression provides an assessment of the prognosis and response to immunotherapy. To illustrate, classification of breast cancer into four classes (ranking from ICR4 to ICR1) have shown better levels of immune anti-tumour response in ICR4 tumours, as well as a prolonged survival in comparison to ICR1-3 tumours. Another study have assessed the clinico-biological value of ICR in breast cancer, via the classification of around 8700 breast tumours and assessment of metastasis-free survival and pathological complete response to neoadjuvant chemotherapy. It has been proven that ICR signature is associated with metastasis-free survival and pathological response to chemotherapy. The increased enrichment of immune signature reflects the expression of cells including T cells, cytotoxic T cells, Th-1 cells, CD8+ T cells, Tγδ cells, and APCs; which defines tumours as immune-active and immune-silent. [7] Although being associated with poor-prognosis, the infiltration of immune cells in ICR4 tumours have resulted in a longer metastasis-free survival and better response to chemotherapy, proving the importance of immune reaction in breast cancer. It was also shown that ICR classification is dependent upon intrinsic molecular subtype of breast tumours, being highly present in triple-negative and HER2+ tumours. === Colon Cancer === A cohort of fresh-frozen samples from 348 patients affected by primary colon cancer (AC-ICAM) was used for genomic examination. this examination revealed that a TH1 cell/cytotoxic immune activation, as captured by the ICR, immunoediting, concurrent expansion of TCR clonotypes and specific intratumoral microbiome composition, were associated with a favorable clinical outcome. The results also revealed that the ICR was associated with overall survival independently of Consensus Molecular Subtypes (CMS) and microsatellite instability (MSI). In addition, they identified a microbiome signature with strong prognostic value (MBR
|
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risk score). The researchers then combined the ICR with the MBR risk score to get a new multi-omics biomarker (mICRoScore) that was able to predict exceptionally long survival in patients with colon cancer. ==== Pancancer ==== A pre-existing intratumoral anti-tumor T helper (Th-1) immune response has been linked to favorable outcomes with immunotherapy, but not all immunologically active cancers respond to treatment. In a pan-cancer analysis using The Cancer Genome Atlas (TCGA) including 31 cancer types from 9282 patients, high expression of the ICR signature was associated with significant prolonged survival in breast invasive carcinoma, skin cutaneous melanoma, sarcoma, and uterine corpus endometrial carcinoma, while this "hot" immune phenotype was associated with reduced overall survival in uveal melanoma, low grade glioma, pancreatic adenocarcinoma and kidney renal clear cell carcinoma. In a systemic analysis, cancer-specific pathways were found to modulate the prognostic value of ICR. In tumors with a high proliferation score, ICR was linked to better survival, while in tumors with low proliferation no association with survival was observed. In tumors dominated by cancer signaling, for example by increased TGF beta signaling, the "hot" immune phenotype did not have any survival benefit, suggesting that the immune response is heavily suppressed without protective effect. The clinical relevance of this finding was demonstrated in the Van Allen dataset with tumor samples of melanoma patients treated with checkpoint inhibitor anti-CTLA4. Overall, a significantly increased expression of ICR was observed in responders compared to non-responders. However, an association of high ICR scores pretreatment with survival was only observed for samples with high proliferation scores. Conversely, ICR was only associated with survival in samples with low TGF beta expression. === Soft tissue sarcoma === In soft tissue sarcoma, a cohort of 1455 non-metastatic samples had the ICR retrospectively applied to them to discover links between
|
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ICR classes and clinicopathological and biological variables. Because of this, the cohort was thus divided into 4 groups labelled as ICR1, ICR2, ICR3 and ICR4 with each consisting of 34, 27, 24, and 15% of the tumors. The aforementioned groups were created while taking into account the age age, pathology depth, and enrichment value ICR1 through 4 of quantitative/qualitative scores of immune responses. When ICR1 is compared to ICR2-4 classes, there was an increase of 59% of metastatic relapse. Multivariate analysis also showed that the ICR classification remained associated with MFS as well as pathological type and CINSARC classification, suggesting that there is an independent prognostic value. The presence of an ICR signature is linked to postoperative MFS in early-stage STS, regardless of other prognostic factors such as CINSARC. A prognostic clinicogenomic model was created which combines ICR, CINSARC, and pathological type to provide a reliable prediction of outcomes. Additionally, the study proposes that each prognostic group has varying levels of susceptibility to different systemic therapies. === Pediatric Cancers === A large a systematic analysis of public RNAseq data (TARGET) for five pediatric tumor types: osteosarcoma (OS), neuroblastoma (NBL), clear cell sarcoma of the kidney (CCSK), Wilms tumor (WLM) and rhabdoid tumor of the kidney (RT) showed a very important role of ICR in pediatric tumors. It was discovered that a lower ICR score was associated with lower survival in WLM while higher ICR score was associated with a better survival in OS and high risk NBL without MYCN amplification. Immune traits were then used to cluster the samples into 6 different immune subtypes (S1-S6) with each having different and distinct survival outcomes. For example, the S2 cluster illustrated the highest overall survival, distinguished by low enrichment of the wound healing signature, high Th1, and low Th2 infiltration. However, the
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opposite was highlighted in S4. Upregulation of the WNT/Beta-catenin pathway was associated with unfavorable outcomes and decreased T-cell infiltration in OS. === Other diseases === Molecular pathways including IFN-stimulated genes activation; the recruitment of NK cells and T cells, by the secretion of CCL5 and CXCL9-10; and the induction of immune effector mechanisms are found overlapping in conditions like autoimmunity, as a results of host-against-self reaction, where immune cells initiate tissue-specific destruction. Similarly, allografting results in a strong immune response, which clinically necessitates a continued immunosuppression to maintain graft survival. They are found to express conformational epitopes, such as MHC molecules, as nonself antigens, which activates both B and T cells. == Alternatives and Variations == === T cell–inflamed GEP or Tumor Inflammation Signature (TIS) === An 18-gene Gene Expression Profile that predicted response to pembrolizumab across multiple solid tumors. Can be used with a platform such as the NanoString nCounter platform and define tumor type–independent dimensions of the tumor microenvironment relevant to predicting clinical outcome for agents targeting the PD-1/PD-L1 signaling pathway. Gene Signature : CCL5, CD27, CD274 (PD-L1), CD276 (B7-H3), CD8A, CMKLR1, CXCL9, CXCR6, HLA-DQA1, HLA-DRB1, HLA-E, IDO1, LAG3, NKG7, PDCD1LG2 (PDL2), PSMB10, STAT1, and TIGIT. === Cytolytic Activity Score (CYT) === A simple 2 gene mean expression score of GZMA and PRF1 expression. High CYT within colorectal cancer is associated with improved survival, likely due to increased immunity and cytolytic activity of T cells and M1 macrophages. The 5-year recurrence-free survival of liver cancer patients with low CYT scores was significantly shorter than that of patients with high CYT scores. === 3-lncRNA Signature === researchers found 20 different 20 lnc-RNA prognostic signatures that showed a stronger effect on overall survival than the ICR signature in different solid cancers. They also found a 3 lncRNA signature that displayed
|
{
"page_id": 52956862,
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prognostic significance in 5 solid cancer types with a stronger association to clinical outcome than ICR and displayed addition prognostic significance in the uterine cohort, endometrial carcinoma, cervical squamous cell carcinomam and endocervical adenocarcinoma as compared to ICR. == References ==
|
{
"page_id": 52956862,
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"title": "Immunologic constant of rejection"
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The molecular formula C41H67NO15 (molar mass: 813.968 g/mol, exact mass: 813.4511 u) may refer to: Midecamycin Troleandomycin (TAO)
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{
"page_id": 24710853,
"source": null,
"title": "C41H67NO15"
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The molecular formula C10H16O4 (molar mass: 200.23 g/mol, exact mass: 200.1049 u) may refer to: Camphoric acid 2-Decendioic acid
|
{
"page_id": 28446406,
"source": null,
"title": "C10H16O4"
}
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The stochastic block model is a generative model for random graphs. This model tends to produce graphs containing communities, subsets of nodes characterized by being connected with one another with particular edge densities. For example, edges may be more common within communities than between communities. Its mathematical formulation was first introduced in 1983 in the field of social network analysis by Paul W. Holland et al. The stochastic block model is important in statistics, machine learning, and network science, where it serves as a useful benchmark for the task of recovering community structure in graph data. == Definition == The stochastic block model takes the following parameters: The number n {\displaystyle n} of vertices; a partition of the vertex set { 1 , … , n } {\displaystyle \{1,\ldots ,n\}} into disjoint subsets C 1 , … , C r {\displaystyle C_{1},\ldots ,C_{r}} , called communities; a symmetric r × r {\displaystyle r\times r} matrix P {\displaystyle P} of edge probabilities. The edge set is then sampled at random as follows: any two vertices u ∈ C i {\displaystyle u\in C_{i}} and v ∈ C j {\displaystyle v\in C_{j}} are connected by an edge with probability P i j {\displaystyle P_{ij}} . An example problem is: given a graph with n {\displaystyle n} vertices, where the edges are sampled as described, recover the groups C 1 , … , C r {\displaystyle C_{1},\ldots ,C_{r}} . == Special cases == If the probability matrix is a constant, in the sense that P i j = p {\displaystyle P_{ij}=p} for all i , j {\displaystyle i,j} , then the result is the Erdős–Rényi model G ( n , p ) {\displaystyle G(n,p)} . This case is degenerate—the partition into communities becomes irrelevant—but it illustrates a close relationship to the Erdős–Rényi model. The
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planted partition model is the special case that the values of the probability matrix P {\displaystyle P} are a constant p {\displaystyle p} on the diagonal and another constant q {\displaystyle q} off the diagonal. Thus two vertices within the same community share an edge with probability p {\displaystyle p} , while two vertices in different communities share an edge with probability q {\displaystyle q} . Sometimes it is this restricted model that is called the stochastic block model. The case where p > q {\displaystyle p>q} is called an assortative model, while the case p < q {\displaystyle p<q} is called disassortative. Returning to the general stochastic block model, a model is called strongly assortative if P i i > P j k {\displaystyle P_{ii}>P_{jk}} whenever j ≠ k {\displaystyle j\neq k} : all diagonal entries dominate all off-diagonal entries. A model is called weakly assortative if P i i > P i j {\displaystyle P_{ii}>P_{ij}} whenever i ≠ j {\displaystyle i\neq j} : each diagonal entry is only required to dominate the rest of its own row and column. Disassortative forms of this terminology exist, by reversing all inequalities. For some algorithms, recovery might be easier for block models with assortative or disassortative conditions of this form. == Typical statistical tasks == Much of the literature on algorithmic community detection addresses three statistical tasks: detection, partial recovery, and exact recovery. === Detection === The goal of detection algorithms is simply to determine, given a sampled graph, whether the graph has latent community structure. More precisely, a graph might be generated, with some known prior probability, from a known stochastic block model, and otherwise from a similar Erdos-Renyi model. The algorithmic task is to correctly identify which of these two underlying models generated the graph. === Partial recovery ===
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"page_id": 47845063,
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In partial recovery, the goal is to approximately determine the latent partition into communities, in the sense of finding a partition that is correlated with the true partition significantly better than a random guess. === Exact recovery === In exact recovery, the goal is to recover the latent partition into communities exactly. The community sizes and probability matrix may be known or unknown. == Statistical lower bounds and threshold behavior == Stochastic block models exhibit a sharp threshold effect reminiscent of percolation thresholds. Suppose that we allow the size n {\displaystyle n} of the graph to grow, keeping the community sizes in fixed proportions. If the probability matrix remains fixed, tasks such as partial and exact recovery become feasible for all non-degenerate parameter settings. However, if we scale down the probability matrix at a suitable rate as n {\displaystyle n} increases, we observe a sharp phase transition: for certain settings of the parameters, it will become possible to achieve recovery with probability tending to 1, whereas on the opposite side of the parameter threshold, the probability of recovery tends to 0 no matter what algorithm is used. For partial recovery, the appropriate scaling is to take P i j = P ~ i j / n {\displaystyle P_{ij}={\tilde {P}}_{ij}/n} for fixed P ~ {\displaystyle {\tilde {P}}} , resulting in graphs of constant average degree. In the case of two equal-sized communities, in the assortative planted partition model with probability matrix P = ( p ~ / n q ~ / n q ~ / n p ~ / n ) , {\displaystyle P=\left({\begin{array}{cc}{\tilde {p}}/n&{\tilde {q}}/n\\{\tilde {q}}/n&{\tilde {p}}/n\end{array}}\right),} partial recovery is feasible with probability 1 − o ( 1 ) {\displaystyle 1-o(1)} whenever ( p ~ − q ~ ) 2 > 2 ( p ~ + q ~ ) {\displaystyle
|
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"page_id": 47845063,
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({\tilde {p}}-{\tilde {q}})^{2}>2({\tilde {p}}+{\tilde {q}})} , whereas any estimator fails partial recovery with probability 1 − o ( 1 ) {\displaystyle 1-o(1)} whenever ( p ~ − q ~ ) 2 < 2 ( p ~ + q ~ ) {\displaystyle ({\tilde {p}}-{\tilde {q}})^{2}<2({\tilde {p}}+{\tilde {q}})} . For exact recovery, the appropriate scaling is to take P i j = P ~ i j log n / n {\displaystyle P_{ij}={\tilde {P}}_{ij}\log n/n} , resulting in graphs of logarithmic average degree. Here a similar threshold exists: for the assortative planted partition model with r {\displaystyle r} equal-sized communities, the threshold lies at p ~ − q ~ = r {\displaystyle {\sqrt {\tilde {p}}}-{\sqrt {\tilde {q}}}={\sqrt {r}}} . In fact, the exact recovery threshold is known for the fully general stochastic block model. == Algorithms == In principle, exact recovery can be solved in its feasible range using maximum likelihood, but this amounts to solving a constrained or regularized cut problem such as minimum bisection that is typically NP-complete. Hence, no known efficient algorithms will correctly compute the maximum-likelihood estimate in the worst case. However, a wide variety of algorithms perform well in the average case, and many high-probability performance guarantees have been proven for algorithms in both the partial and exact recovery settings. Successful algorithms include spectral clustering of the vertices, semidefinite programming, forms of belief propagation, and community detection among others. == Variants == Several variants of the model exist. One minor tweak allocates vertices to communities randomly, according to a categorical distribution, rather than in a fixed partition. More significant variants include the degree-corrected stochastic block model, the hierarchical stochastic block model, the geometric block model, censored block model and the mixed-membership block model. == Topic models == Stochastic block model have been recognised to be a topic
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"page_id": 47845063,
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model on bipartite networks. In a network of documents and words, Stochastic block model can identify topics: group of words with a similar meaning. == Extensions to signed graphs == Signed graphs allow for both favorable and adverse relationships and serve as a common model choice for various data analysis applications, e.g., correlation clustering. The stochastic block model can be trivially extended to signed graphs by assigning both positive and negative edge weights or equivalently using a difference of adjacency matrices of two stochastic block models. == DARPA/MIT/AWS Graph Challenge: streaming stochastic block partition == GraphChallenge encourages community approaches to developing new solutions for analyzing graphs and sparse data derived from social media, sensor feeds, and scientific data to enable relationships between events to be discovered as they unfold in the field. Streaming stochastic block partition is one of the challenges since 2017. Spectral clustering has demonstrated outstanding performance compared to the original and even improved base algorithm, matching its quality of clusters while being multiple orders of magnitude faster. == See also == blockmodeling Girvan–Newman algorithm – Community detection algorithm Lancichinetti–Fortunato–Radicchi benchmark – AlgorithmPages displaying short descriptions with no spaces for generating benchmark networks with communities == References ==
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"page_id": 47845063,
"source": null,
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The Coolgardie safe is a low-tech food storage unit, using evaporative cooling to prolong the life of whatever edibles are kept in it. It applies the basic principle of heat transfer which occurs during evaporation of water (see latent heat and heat of evaporation). It was named after the place where it was invented – the small mining town of Coolgardie, Western Australia, near Kalgoorlie-Boulder. == History == Coolgardie was the site of a gold rush in the early 1890s, before the Kalgoorlie-Boulder gold rush. For the prospectors who had rushed here to find their fortune, one challenge was to extend the life of their perishable foods – hence the invention of the Coolgardie safe. The safe was invented in the late 1890s by Arthur Patrick McCormick, who used the same principle as explorers and travellers in the Outback used to cool their canvas water bags: when the canvas bag is wet the fibres expand and it holds water. Some water seeps out and evaporates. It is most effective when air continually moves past it, such as when in a moving vehicle or when exposed to a breeze. This technology is commonly thought to have been adopted by explorer and scientist Thomas Mitchell, who had observed the way some Indigenous Australians used kangaroo skins to carry water. == Principles of operation == The Coolgardie safe was made of wire mesh, hessian, a wooden frame and had a hot dip galvanised iron tray on top. The galvanised iron tray was filled with water. The hessian bag was hung over the side with one of the ends in the tray to soak up the water. Gradually the hessian bag, acting as a wick, would draw water from the tray by the process of capillary action. When a breeze came it would pass
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"page_id": 2297543,
"source": null,
"title": "Coolgardie safe"
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through the wet bag and evaporate the water. This would cool the air inside the safe, and in turn cool the food stored in the safe. This cooling is due to the water in the hessian needing energy to change state and evaporate. This energy is taken from the interior of the safe (metal mesh), thus making the interior cooler. There is a metal tray below the safe to catch excess water from the hessian. Some modern tests have shown that the interior of the safe would achieve temperatures 3–9 °C (dependant on breeze) cooler than the atmospheric temperature during the middle of the day. It was usually placed on a veranda where there was a breeze. The Coolgardie safe was a common household item in Australia until the mid-twentieth century. Safes could be purchased ready-made or easily constructed at home. Some of the metal panel safes are highly decorated. == See also == Icebox Zeer pot Solar powered refrigerator Evaporative cooling == References ==
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{
"page_id": 2297543,
"source": null,
"title": "Coolgardie safe"
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A standing crop is the total biomass of the living organisms present in a given environment. This includes both natural ecosystems and agriculture. == See also == Net Primary Production Standing State == Bibliography == Ackley, S. F.; Buck, K. R.; Taguchi, S. (1979). "Standing crop of algae in the sea ice of the Weddell Sea region". Deep-Sea Research Part A: Oceanographic Research Papers. 26 (3): 269–281. Bibcode:1979DSRA...26..269A. doi:10.1016/0198-0149(79)90024-4. Boudouresque CF (1973) Les peuplements sciaphiles; Recherches de bionomie analytique, structurale et expérimentale sur les peuplements benthiques sciaphiles de Méditerranée occidentale (fraction algale). Bulletin du Muséum d'histoire naturelle, 33, 147, PDF, 80 pages. Campbell, Reece, Urry, Cain, et al. (2011) 9th ed. Biology. Benjamin Cummings. pg 1221 Fausch, K. D., Hawkes, C. L., & Parsons, M. G. (1988). Models that predict standing crop of stream fish from habitat variables: 1950-85 (http://www.treesearch.fs.fed.us/pubs/8730 résumé]). Hatcher, B. G.; Larkum, A. W. D. (1983). "An experimental analysis of factors controlling the standing crop of the epilithic algal community on a coral reef". Journal of Experimental Marine Biology and Ecology. 69 (1): 61–84. doi:10.1016/0022-0981(83)90172-7. Jenkins, R. M. (1968). The influence of some environmental factors on standing crop and harvest of fishes in US reservoirs. Moore, D. R.; Keddy, P. A. (1988). "The relationship between species richness and standing crop in wetlands: the importance of scale". Vegetatio. 79 (1–2): 99–106. doi:10.1007/BF00044853. S2CID 2448402. Oglesby, R. T. (1977). "Relationships of fish yield to lake phytoplankton standing crop, production, and morphoedaphic factors". Journal of the Fisheries Board of Canada. 34 (12): 2271–2279. doi:10.1139/f77-305. Schindler, D. W. (1978). "Factors regulating phytoplankton production and standing crop in the world's freshwaters" (PDF). Limnol. Oceanogr. 23 (3): 478–486. Bibcode:1978LimOc..23..478S. doi:10.4319/lo.1978.23.3.0478. Schindler, D. W.; Fee, E. J.; Ruszczynski, T. (1978). "Phosphorus input and its consequences for phytoplankton standing crop and production in the Experimental
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"page_id": 13438665,
"source": null,
"title": "Standing crop"
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Lakes Area and in similar lakes". Journal of the Fisheries Board of Canada. 35 (2): 190–196. doi:10.1139/f78-031. Williams, R. B.; Murdoch, M. B.; Thomas, L. K. (1968). "Standing crop and importance of zooplankton in a system of shallow estuaries". Chesapeake Science. 9 (1): 42–51. doi:10.2307/1351282. JSTOR 1351282. == References == == External links == Models that predict standing crop of stream fish from habitat variables: 1950-85
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"page_id": 13438665,
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Brassica rapa is a plant species that has been widely cultivated into many forms, including the turnip (a root vegetable), komatsuna, napa cabbage, bomdong, bok choy, and rapini. Brassica rapa subsp. oleifera is an oilseed commonly known as turnip rape, field mustard, bird's rape, and keblock. Rapeseed oil is a general term for oil from some Brassica species. Food grade oil made from the seed of low-erucic acid Canadian-developed strains is also called canola oil, while non-food oil is called colza oil. Canola oil can be sourced from Brassica rapa and Brassica napus, which are commonly grown in Canada, and Brassica juncea, which is less common. == History == The geographic and genetic origins of B. rapa have been difficult to identify due to its long history of human cultivation. It is found in most parts of the world, and has returned to the wild many times as a feral plant or weed. Genetic sequencing and environmental modelling have indicated that ancestral B. rapa likely originated 4000 to 6000 years ago in the Hindu Kush area of Central Asia, and had three sets of chromosomes, providing the genetic potential for a diversity of form, flavour, and growth. Domestication has produced modern vegetables and oil-seed crops, all with two sets of chromosomes. Oilseed subspecies (subsp. oleifera) of Brassica rapa may have been domesticated several times from the Mediterranean to India, starting as early as 2000 BC. There are descriptions of B. rapa vegetables in Indian and Chinese documents from around 1000 BC. Edible turnips were possibly first cultivated in northern Europe, and were an important food in ancient Rome. The turnip then spread east to China, and reached Japan by 700 AD. In the 18th century, the turnip and the oilseed-producing variants were thought to be different species by Carl Linnaeus,
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{
"page_id": 1904332,
"source": null,
"title": "Brassica rapa"
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|
who named them B. rapa and B. campestris. Twentieth-century taxonomists found that the plants were cross fertile and thus belonged to the same species. Since the turnip had been named first by Linnaeus, the name Brassica rapa was adopted. == Uses == Many butterflies, including the small white, feed from and pollinate the B. rapa flowers. The young leaves are a common leaf vegetable and can be eaten raw; older leaves are typically cooked. The taproot and seeds can also be eaten raw, although the seeds contain an oil that can cause irritation for some people. == Cultivars == == References == == External links == Media related to Brassica rapa at Wikimedia Commons " Multilingual taxonomic information". University of Melbourne. PROTA (Plant Resources of Tropical Africa) database record on Brassica rapa L.
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{
"page_id": 1904332,
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"title": "Brassica rapa"
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The Marie Curie-Skłodowska Medal is a Polish annual science award conferred by the Polish Chemical Society (Polish: Polskie Towarzystwo Chemiczne, PTCHem) to scientists working permanently abroad for contributions in the field of chemistry. == Description == It was named in honour of physicist Marie Curie (1867–1934) and first awarded in 1996. The winner receives a bronze medal depicting Marie Curie and on the reverse the Latin inscription Quo Magis Veritas Propagatur as well as the PTCHem logo, year and the name of the laureate. Four laureates of the medal have also been awarded the Nobel Prize in Chemistry: Roald Hoffmann (1981), Jean Marie Lehn (1987), Ada Yonath (2009) and Ben Feringa (2016). == Laureates == The winners of the award so far have been: == Notes == a Sites of the work places of the Laureates at the time of the award. == See also == Prize of the Foundation for Polish Science Marian Smoluchowski Medal Kołos Medal == References ==
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"page_id": 63180494,
"source": null,
"title": "Marie Curie Medal"
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FICO (legal name: Fair Isaac Corporation), originally Fair, Isaac and Company, is an American data analytics company based in Bozeman, Montana, focused on credit scoring services. It was founded by Bill Fair and Earl Isaac in 1956. Its FICO score, a measure of consumer credit risk, has become a fixture of consumer lending in the United States. In 2013, lenders purchased more than 10 billion FICO scores and about 30 million American consumers accessed their scores themselves. The company reported a revenue of $1.29 billion for the fiscal year of 2020. == History == FICO was founded in 1956 as Fair, Isaac and Company by engineer William R. "Bill" Fair and mathematician Earl Judson Isaac. The two met while working at the Stanford Research Institute in Menlo Park, California. Selling its first credit scoring system two years after the company's creation, FICO pitched its system to fifty American lenders. FICO went public in July 1987 and is traded on the New York Stock Exchange. The company debuted its first general-purpose FICO score in 1989. FICO scores are based on credit reports and "base" FICO scores range from 300 to 850, while industry-specific scores range from 250 to 900. Lenders use the scores to gauge a potential borrower's creditworthiness. Fannie Mae and Freddie Mac first began using FICO scores to help determine which American consumers qualified for mortgages bought and sold by the companies in 1995. === Name changes === Originally called Fair, Isaac and Company (hence the abbreviation FICO), this name was changed to Fair Isaac Corporation in 2003. === Headquarters moves === Originally based in San Rafael, California, FICO moved its headquarters to Minneapolis, Minnesota, in 2004, a few years after Minnesota resident Thomas Grudnowski took over as CEO. In 2013, it moved its headquarters to San Jose, California,
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"title": "FICO"
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a year after CEO William Lansing joined. In 2016 it opened an office in Bozeman, Montana which later became its headquarters. == Acquisitions == DynaMark 1992 Risk Management Technologies 1997 Prevision 1997 Nykamp Consulting Group 2001 HNC Software 2002 NAREX 2003 Diversified Healthcare Services 2003 Seurat (2003) London Bridge Software 2004 Braun Consulting 2004 RulesPower 2005 Dash Optimization 2008 Entiera 2012 Adeptra 2012 CR Software 2012 Infoglide 2013 InfoCentricity 2014 Karmasphere 2014 TONBELLER AG 2015 QuadMetrics 2016 GoOn 2018 EZMCOM 2019 == Antitrust issues == In March 2020, the US Department of Justice (DOJ) opened an antitrust investigation into FICO, which was reported to be closed in December 2020. In March 2024, US Senator Josh Hawley sent a letter to the DOJ's Antitrust Division urging them to open an investigation into FICO for anti-competitive practices, stating that the company "appears to be using its monopolistic power over the credit scoring market to increase costs for mortgage lenders." Between 2020 and 2023, at least 10 antitrust class action lawsuits were filed against FICO involving "business to business" purchases of FICO scores, with the plaintiffs alleging that FICO maintains monopoly power through anticompetitive agreements and charges artificially inflated prices for FICO scores. In September 2023 US District Judge Edmond Chang ruled that the plaintiffs, which include credit unions, banks, mortgage lenders, real estate brokerages, auto dealers, and other companies, had presented enough evidence that FICO had violated antitrust law to allow the lawsuits to proceed. == Operations == FICO is headquartered in Bozeman, Montana and it has additional U.S. locations in San Jose, California, Roseville, Minnesota, San Diego, California, San Rafael, California, Fairfax, Virginia, and Austin, Texas. The company has international locations in Australia, Brazil, Canada, China, Germany, India, Italy, Japan, South Korea, Lithuania, Malaysia, the Philippines, Poland, Russia, Singapore, South Africa,
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"page_id": 462546,
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"title": "FICO"
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Spain, Taiwan, Thailand, Turkey, and the United Kingdom. == FICO score == A measure of credit risk, FICO scores are available through all of the major consumer reporting agencies in the United States: Equifax, Experian, and TransUnion. FICO scores are also offered in other markets, including Mexico and Canada, as well as through the fourth U.S. credit reporting bureau, PRBC. == References == == External links == Official website Business data for Fair Isaac Corporation: How Does FICO Calculate a Score?
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"page_id": 462546,
"source": null,
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A physical system is a collection of physical objects under study. The collection differs from a set: all the objects must coexist and have some physical relationship. In other words, it is a portion of the physical universe chosen for analysis. Everything outside the system is known as the environment, which is ignored except for its effects on the system. The split between system and environment is the analyst's choice, generally made to simplify the analysis. For example, the water in a lake, the water in half of a lake, or an individual molecule of water in the lake can each be considered a physical system. An isolated system is one that has negligible interaction with its environment. Often a system in this sense is chosen to correspond to the more usual meaning of system, such as a particular machine. In the study of quantum coherence, the "system" may refer to the microscopic properties of an object (e.g. the mean of a pendulum bob), while the relevant "environment" may be the internal degrees of freedom, described classically by the pendulum's thermal vibrations. Because no quantum system is completely isolated from its surroundings, it is important to develop a theoretical framework for treating these interactions in order to obtain an accurate understanding of quantum systems. In control theory, a physical system being controlled (a "controlled system") is called a "plant". == See also == Conceptual systems Phase space Physical phenomenon Physical ontology Signal-flow graph Systems engineering Systems science Thermodynamic system Open quantum system == References == == Further reading == Bunge, Mario (13 March 2013). Foundations of Physics. Springer Science & Business Media. ISBN 978-3-642-49287-7. Retrieved 21 June 2023. Bunge, Mario; Mahner, Martin (2004). Über die Natur der Dinge: Materialismus und Wissenschaft (in German). S. Hirzel. ISBN 978-3-7776-1321-5. Halloun, Ibrahim A.
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{
"page_id": 30871250,
"source": null,
"title": "Physical system"
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(25 January 2007). Modeling Theory in Science Education. Springer Science & Business Media. ISBN 978-1-4020-2140-4. Retrieved 21 June 2023. Schmutzer, Ernst (29 August 2005). Grundlagen der Theoretischen Physik (in German). John Wiley & Sons. ISBN 978-3-527-40555-8. Retrieved 21 June 2023.
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{
"page_id": 30871250,
"source": null,
"title": "Physical system"
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The Meaning of Relativity: Four Lectures Delivered at Princeton University, May 1921 is a book published by Princeton University Press in 1922 that compiled the 1921 Stafford Little Lectures at Princeton University, given by Albert Einstein. The lectures were translated into English by Edwin Plimpton Adams. The lectures and the subsequent book were Einstein's last attempt to provide a comprehensive overview of his theory of relativity and is his only book that provides an accessible overview of the physics and mathematics of general relativity. Einstein explained his goal in the preface of the book's German edition by stating he "wanted to summarize the principal thoughts and mathematical methods of relativity theory" and that his "principal aim was to let the fundamentals in the entire train of thought of the theory emerge clearly". Among other reviews, the lectures were the subject of the 2017 book The Formative Years of Relativity: The History and Meaning of Einstein's Princeton Lectures by Hanoch Gutfreund and Jürgen Renn. == Background == The book contains four of Einstein's Stafford Little Lectures that were given at Princeton University in 1921. The lectures follow a series of 1915 publications by Einstein developing the theory of general relativity. During this time, there were still many controversial issues surrounding the theories and he was still defending several of his views. The lectures and the subsequent book were Einstein's last attempt to provide a comprehensive overview of his theory of relativity. It is also his only book that provides an overview of the physics and mathematics of general relativity in a comprehensive manner that was accessible to non-specialists. Einstein explained his goal in the preface of the book's German edition by stating he "wanted to summarize the principal thoughts and mathematical methods of relativity theory" and that his "principal aim was
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"page_id": 65933012,
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to let the fundamentals in the entire train of thought of the theory emerge clearly". On December 27, 1949, The New York Times ran a story titled "New Einstein theory gives a master key to the universe" in reaction to the new appendix in the book's fifth edition in which Einstein expounded upon his latest unification efforts. Einstein had nothing to do with the article and subsequently refused to speak with any reporters on the matter; he reportedly used the message "[c]ome back and see me in twenty years" to brush off their inquiries. == Content == The book is made of four lectures. The first is titled "Space and Time in Pre-Relativity Physics". The second lecture is titled The Theory of Special Relativity and discusses the special theory of relativity. The third and fourth lectures cover the general theory of relativity in two parts. Einstein added an appendix to update the book for its second edition, which published in 1945. A second appendix was later added for the fifth edition as well, in 1955, which discusses the nonsymmetric field. The second appendix contains Einstein's attempts at a unified field theory. == Reception == The book has received many reviews since its initial publication. The first edition of the book was reviewed by Nature in 1923. Other early versions of the book were reviewed by George Yuri Rainich in 1946, as well as Abraham H. Taub, Philip Morrison, and I. M. Levitt in 1950. Reviews for the book's fifth edition include a short announcement in 1955 that called the book "a well-known classic". A 1956 review of the fifth edition summarizes its publication history and contents and closes by stating "Einstein's little book then serves as an excellent tying-together of loose ends and as a broad survey of the subject."
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"page_id": 65933012,
"source": null,
"title": "The Meaning of Relativity"
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Among other references to the book, a 2005 column of The Physics Teacher, included the work in a list of books "by and about Einstein that all physics teachers should have" and "should have immediate access to", while a 2019 review of another work opened by stating: "Every teacher of General Relativity depends heavily on two texts: one, the massive Gravitation by Misner, Thorne and Wheeler, the second the diminutive The Meaning of Relativity by Einstein." The Meaning of Relativity is the focus of a 2017 book, The Formative Years of Relativity by Hanoch Gutfreund and Jürgen Renn, which described The Meaning of Relativity as "Einstein's definitive exposition of his special and general theories of relativity". == Publication history == === Original English editions === Einstein, Albert; Adams, Edwin Plimpton (1922). The Meaning of Relativity: Four Lectures Delivered at Princeton Univ., May, 1921 (1st ed.). London: Methuen Publishing. OCLC 637254801. Einstein, Albert (1945). The Meaning of Relativity (2nd ed.). Princeton, N.J.: Princeton University Press. OCLC 1105547540. Einstein, Albert (1950). The Meaning of Relativity (3rd ed.). Princeton: Princeton University Press. OCLC 1304366. Einstein, Albert (1953). The Meaning of Relativity: Including the Generalization of Gravitation Theory (4th ed.). Princeton, N.J.: Princeton University Press. OCLC 946162394. Einstein, Albert (1955). The meaning of relativity: including the relativistic theory of the non-symmetric field. Princeton: Princeton University Press. ISBN 9780691080079. OCLC 177301011. {{cite book}}: ISBN / Date incompatibility (help) === Notable reprints === Einstein, Albert (1967). The meaning of relativity. Foreword by William Hunter McCrea. Dordrecht: Springer Science+Business Media. ISBN 978-94-011-6022-3. OCLC 858949974. Einstein, Albert (2014). The Meaning of Relativity: Including the Relativistic Theory of the Non-symmetric Field. Introduction by Brian Greene (5th paperback ed.). Princeton: Princeton University Press. ISBN 978-0-6911-6408-3. OCLC 884013779. Einstein, Albert (2014). The Meaning of Relativity: Including the Relativistic Theory of the
|
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"page_id": 65933012,
"source": null,
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Non-symmetric Field. Introduction by Brian Greene (5th eBook ed.). Princeton: Princeton University Press. ISBN 978-1-4008-5187-4. OCLC 884013779. === German editions === Einstein, Albert (1922). Vier Vorlesungen über Relativitätstheorie: gehalten im Mai 1921 an der Universität Princeton (in German). Braunschweig: Friedrich Vieweg. OCLC 2602048. Einstein, Albert (1923). Vier Vorlesungen über Relativitätstheorie: gehalten im Mai 1912 an der Universität Princeton (in German). Braunschweig: Friedrich Vieweg. OCLC 703134729. Einstein, Albert; Bargmann, Valentine (1956). Grundzüge der Relativitätstheorie (in German) (3rd ed.). Friedrich Vieweg. OCLC 73339958. Einstein, Albert (1965). Grundzüge der Relativitätstheorie (in German) (4th ed.). Braunschweig: Friedrich Vieweg. OCLC 257683026. Einstein, Albert; Treder, Hans-Jürgen; Bargmann, Valentine (1969). Grundzüge der Relativitätstheorie (in German). Friedrich Vieweg. ISBN 978-3-528-06058-9. OCLC 263642156. Einstein, Albert (2009). Grundzüge der Relativitätstheorie (in German). Springer Science+Business Media. ISBN 978-3-540-87846-9. OCLC 298553863. == See also == List of scientific publications by Albert Einstein Annus Mirabilis papers History of general relativity History of special relativity == References == == Further reading == == External links == Quotations related to The Meaning of Relativity at Wikiquote The Meaning of Relativity 5th edition at Princeton University Press The Meaning of Relativity 5th edition at JSTOR The Meaning of Relativity at Springer Link An insightful tome recounts the heady early days of general relativity review by Andrew Robinson at sciencemag.org
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}
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Deepfake pornography, or simply fake pornography, is a type of synthetic pornography that is created via altering already-existing photographs or video by applying deepfake technology to the images of the participants. The use of deepfake pornography has sparked controversy because it involves the making and sharing of realistic videos featuring non-consenting individuals and is sometimes used for revenge porn. Efforts are being made to combat these ethical concerns through legislation and technology-based solutions. == History == The term "deepfake" was coined in 2017 on a Reddit forum where users shared altered pornographic videos created using machine learning algorithms. It is a combination of the word "deep learning", which refers to the program used to create the videos, and "fake" meaning the videos are not real. Deepfake pornography was originally created on a small individual scale using a combination of machine learning algorithms, computer vision techniques, and AI software. The process began by gathering a large amount of source material (including both images and videos) of a person's face, and then using a deep learning model to train a Generative Adversarial Network to create a fake video that convincingly swaps the face of the source material onto the body of a pornographic performer. However, the production process has significantly evolved since 2018, with the advent of several public apps that have largely automated the process. Deepfake pornography is sometimes confused with fake nude photography, but the two are mostly different. Fake nude photography typically uses non-sexual images and merely makes it appear that the people in them are nude. == Notable cases == Deepfake technology has been used to create non-consensual and pornographic images and videos of famous women. One of the earliest examples occurred in 2017 when a deepfake pornographic video of Gal Gadot was created by a Reddit user
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"source": null,
"title": "Deepfake pornography"
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and quickly spread online. Since then, there have been numerous instances of similar deepfake content targeting other female celebrities, such as Emma Watson, Natalie Portman, and Scarlett Johansson. Johansson spoke publicly on the issue in December 2018, condemning the practice but also refusing legal action because she views the harassment as inevitable. === Rana Ayyub === In 2018, Rana Ayyub, an Indian investigative journalist, was the target of an online hate campaign stemming from her condemnation of the Indian government, specifically her speaking out against the rape of an eight-year-old Kashmiri girl. Ayyub was bombarded with rape and death threats, and had doctored pornographic video of her circulated online. In a Huffington Post article, Ayyub discussed the long-lasting psychological and social effects this experience has had on her. She explained that she continued to struggle with her mental health and how the images and videos continued to resurface whenever she took a high-profile case. === Atrioc controversy === In 2023, Twitch streamer Atrioc stirred controversy when he accidentally revealed deepfake pornographic material featuring female Twitch streamers while on live. The influencer has since admitted to paying for AI generated porn, and apologized to the women and his fans. === Taylor Swift === In January 2024, AI-generated sexually explicit images of American singer Taylor Swift were posted on X (formerly Twitter), and spread to other platforms such as Facebook, Reddit and Instagram. One tweet with the images was viewed over 45 million times before being removed. A report from 404 Media found that the images appeared to have originated from a Telegram group, whose members used tools such as Microsoft Designer to generate the images, using misspellings and keyword hacks to work around Designer's content filters. After the material was posted, Swift's fans posted concert footage and images to bury the
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{
"page_id": 62590682,
"source": null,
"title": "Deepfake pornography"
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deepfake images, and reported the accounts posting the deepfakes. Searches for Swift's name were temporarily disabled on X, returning an error message instead. Graphika, a disinformation research firm, traced the creation of the images back to a 4chan community. A source close to Swift told the Daily Mail that she would be considering legal action, saying, "Whether or not legal action will be taken is being decided, but there is one thing that is clear: These fake AI-generated images are abusive, offensive, exploitative, and done without Taylor's consent and/or knowledge." The controversy drew condemnation from White House Press Secretary Karine Jean-Pierre, Microsoft CEO Satya Nadella, the Rape, Abuse & Incest National Network, and SAG-AFTRA. Several US politicians called for federal legislation against deepfake pornography. Later in the month, US senators Dick Durbin, Lindsey Graham, Amy Klobuchar and Josh Hawley introduced a bipartisan bill that would allow victims to sue individuals who produced or possessed "digital forgeries" with intent to distribute, or those who received the material knowing it was made non-consensually. === 2024 Telegram deepfake scandal === It emerged in South Korea in August 2024, that many teachers and female students were victims of deepfake images created by users who utilized AI technology. Journalist Ko Narin of The Hankyoreh uncovered the deepfake images through Telegram chats. On Telegram, group chats were created specifically for image-based sexual abuse of women, including middle and high school students, teachers, and even family members. Women with photos on social media platforms like KakaoTalk, Instagram, and Facebook are often targeted as well. Perpetrators use AI bots to generate fake images, which are then sold or widely shared, along with the victims’ social media accounts, phone numbers, and KakaoTalk usernames. One Telegram group reportedly drew around 220,000 members, according to a Guardian report. Investigations revealed numerous
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{
"page_id": 62590682,
"source": null,
"title": "Deepfake pornography"
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chat groups on Telegram where users, mainly teenagers, create and share explicit deepfake images of classmates and teachers. The issue came in the wake of a troubling history of digital sex crimes, notably the notorious Nth Room case in 2019. The Korean Teachers Union estimated that more than 200 schools had been affected by these incidents. Activists called for a "national emergency" declaration to address the problem. South Korean police reported over 800 deepfake sex crime cases by the end of September 2024, a stark rise from just 156 cases in 2021, with most victims and offenders being teenagers. On September 21, 6,000 people gathered at Marronnier Park in northeastern Seoul to demand stronger legal action against deepfake crimes targeting women. On September 26, following widespread outrage over the Telegram scandal, South Korean lawmakers passed a bill criminalizing the possession or viewing of sexually explicit deepfake images and videos, imposing penalties that include prison terms and fines. Under the new law, those caught buying, saving, or watching such material could face up to three years in prison or fines up to 30 million won ($22,600). At the time the bill was proposed, creating sexually explicit deepfakes for distribution carried a maximum penalty of five years, but the new legislation would increase this to seven years, regardless of intent. By October 2024, it was estimated that "nudify" deep fake bots on Telegram were up to four million monthly users. == Ethical considerations == === Deepfake child pornography === Deepfake technology has made the creation of child pornography, faster and easier than it has ever been. Deepfakes can be used to produce new child pornography from already existing material or creating pornography from children who have not been subjected to sexual abuse. Deepfake child pornography can, however, have real and direct implications
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{
"page_id": 62590682,
"source": null,
"title": "Deepfake pornography"
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on children including defamation, grooming, extortion, and bullying. === Differences from generative AI pornography === While both deepfake pornography and generative AI pornography utilize synthetic media, they differ in approach and ethical implications. Generative AI pornography is created entirely through algorithms, producing hyper-realistic content unlinked to real individuals. In contrast, Deepfake pornography alters existing footage of real individuals, often without consent, by superimposing faces or modifying scenes. Hany Farid, a digital image analysis expert, has emphasized these distinctions. === Consent === Most deepfake pornography is made using the faces of people who did not consent to their image being used in such a sexual way. In 2023, Sensity, an identify verification company, has found that "96% of deepfakes are sexually explicit and feature women who didn’t consent to the creation of the content." == Combatting deepfake pornography == === Technical approach === Deepfake detection has become an increasingly important area of research in recent years as the spread of fake videos and images has become more prevalent. One promising approach to detecting deepfakes is through the use of Convolutional Neural Networks (CNNs), which have shown high accuracy in distinguishing between real and fake images. One CNN-based algorithm that has been developed specifically for deepfake detection is DeepRhythm, which has demonstrated an impressive accuracy score of 0.98 (i.e. successful at detecting deepfake images 98% of the time). This algorithm utilizes a pre-trained CNN to extract features from facial regions of interest and then applies a novel attention mechanism to identify discrepancies between the original and manipulated images. While the development of more sophisticated deepfake technology presents ongoing challenges to detection efforts, the high accuracy of algorithms like DeepRhythm offers a promising tool for identifying and mitigating the spread of harmful deepfakes. Aside from detection models, there are also video authenticating tools
|
{
"page_id": 62590682,
"source": null,
"title": "Deepfake pornography"
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|
available to the public. In 2019, Deepware launched the first publicly available detection tool which allowed users to easily scan and detect deepfake videos. Similarly, in 2020 Microsoft released a free and user-friendly video authenticator. Users upload a suspected video or input a link, and receive a confidence score to assess the level of manipulation in a deepfake. === Legal approach === As of 2023, there is a lack of legislation that specifically addresses deepfake pornography. Instead, the harm caused by its creation and distribution is being addressed by the courts through existing criminal and civil laws. Victims of deepfake pornography often have claims for revenge porn, tort claims, and harassment. The legal consequences for revenge porn vary from state to state and country to country. For instance, in Canada, the penalty for publishing non-consensual intimate images is up to 5 years in prison, whereas in Malta it is a fine of up to €5,000. The "Deepfake Accountability Act" was introduced to the United States Congress in 2019 but died in 2020. It aimed to make the production and distribution of digitally altered visual media that was not disclosed to be such, a criminal offense. The title specifies that making any sexual, non-consensual altered media with the intent of humiliating or otherwise harming the participants, may be fined, imprisoned for up to 5 years or both. A newer version of bill was introduced in 2021 which would have required any "advanced technological false personation records" to contain a watermark and an audiovisual disclosure to identify and explain any altered audio and visual elements. The bill also includes that failure to disclose this information with intent to harass or humiliate a person with an "advanced technological false personation record" containing sexual content "shall be fined under this title, imprisoned for not
|
{
"page_id": 62590682,
"source": null,
"title": "Deepfake pornography"
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more than 5 years, or both." However this bill has since died in 2023. In the United Kingdom, the Law Commission for England and Wales recommended reform to criminalise sharing of deepfake pornography in 2022. In 2023, the government announced amendments to the Online Safety Bill to that end. The Online Safety Act 2023 amends the Sexual Offences Act 2003 to criminalise sharing intimate images that shows or "appears to show" another (thus including deepfake images) without consent. In 2024, the Government announced that an offence criminalising the production of deepfake pornographic images would be included in the Criminal Justice Bill of 2024. The Bill did not pass before Parliament was dissolved before the general election. In South Korea, the creation, distribution, or possession of deepfake pornography is classified as a sex crime, with a mandatory prison sentence between three to seven years as part of the country's Special Act on Sexual Violence Crimes. ==== Controlling the distribution ==== While the legal landscape remains undeveloped, victims of deepfake pornography have several tools available to contain and remove content, including securing removal through a court order, intellectual property tools like the DMCA takedown, reporting for terms and conditions violations of the hosting platform, and removal by reporting the content to search engines. Several major online platforms have taken steps to ban deepfake pornography. As of 2018, gfycat, reddit, Twitter, Discord, and Pornhub have all prohibited the uploading and sharing of deepfake pornographic content on their platforms. In September of that same year, Google also added "involuntary synthetic pornographic imagery" to its ban list, allowing individuals to request the removal of such content from search results. == See also == Fake nude photography Revenge porn Another Body, 2023 documentary film about a student's quest for justice after finding deepfake pornography of herself
|
{
"page_id": 62590682,
"source": null,
"title": "Deepfake pornography"
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online == References ==
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{
"page_id": 62590682,
"source": null,
"title": "Deepfake pornography"
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A body plan, Bauplan (pl. German: Baupläne), or ground plan is a set of morphological features common to many members of a phylum of animals. The vertebrates share one body plan, while invertebrates have many. This term, usually applied to animals, envisages a "blueprint" encompassing aspects such as symmetry, layers, segmentation, nerve, limb, and gut disposition. Evolutionary developmental biology seeks to explain the origins of diverse body plans. Body plans have historically been considered to have evolved in a flash in the Ediacaran biota; filling the Cambrian explosion with the results, and a more nuanced understanding of animal evolution suggests gradual development of body plans throughout the early Palaeozoic. Recent studies in animals and plants started to investigate whether evolutionary constraints on body plan structures can explain the presence of developmental constraints during embryogenesis such as the phenomenon referred to as phylotypic stage. == History == Among the pioneering zoologists, Linnaeus identified two body plans outside the vertebrates; Cuvier identified three; and Haeckel had four, as well as the Protista with eight more, for a total of twelve. For comparison, the number of phyla recognised by modern zoologists has risen to 36. === Linnaeus, 1735 === In his 1735 book Systema Naturæ, Swedish botanist Linnaeus grouped the animals into quadrupeds, birds, "amphibians" (including tortoises, lizards and snakes), fish, "insects" (Insecta, in which he included arachnids, crustaceans and centipedes) and "worms" (Vermes). Linnaeus's Vermes included effectively all other groups of animals, not only tapeworms, earthworms and leeches but molluscs, sea urchins and starfish, jellyfish, squid and cuttlefish. === Cuvier, 1817 === In his 1817 work, Le Règne Animal, French zoologist Georges Cuvier combined evidence from comparative anatomy and palaeontology to divide the animal kingdom into four body plans. Taking the central nervous system as the main organ system which controlled all
|
{
"page_id": 4394717,
"source": null,
"title": "Body plan"
}
|
the others, such as the circulatory and digestive systems, Cuvier distinguished four body plans or embranchements: Grouping animals with these body plans resulted in four branches: vertebrates, molluscs, articulata (including insects and annelids) and zoophytes or Radiata. === Haeckel, 1866 === Ernst Haeckel, in his 1866 Generelle Morphologie der Organismen, asserted that all living things were monophyletic (had a single evolutionary origin), being divided into plants, protista, and animals. His protista were divided into moneres, protoplasts, flagellates, diatoms, myxomycetes, myxocystodes, rhizopods, and sponges. His animals were divided into groups with distinct body plans: he named these phyla. Haeckel's animal phyla were coelenterates, echinoderms, and (following Cuvier) articulates, molluscs, and vertebrates. === Gould, 1979 === Stephen J. Gould explored the idea that the different phyla could be perceived in terms of a Bauplan, illustrating their fixity. However, he later abandoned this idea in favor of punctuated equilibrium. == Origin == 20 out of the 36 body plans originated in the Cambrian period, in the "Cambrian explosion". However, complete body plans of many phyla emerged much later, in the Palaeozoic or beyond. The current range of body plans is far from exhaustive of the possible patterns for life: the Precambrian Ediacaran biota includes body plans that differ from any found in currently living organisms, even though the overall arrangement of unrelated modern taxa is quite similar. Thus the Cambrian explosion appears to have more or less completely replaced the earlier range of body plans. == Genetic basis == Genes, embryos and development together determine the form of an adult organism's body, through the complex switching processes involved in morphogenesis. Developmental biologists seek to understand how genes control the development of structural features through a cascade of processes in which key genes produce morphogens, chemicals that diffuse through the body to produce a
|
{
"page_id": 4394717,
"source": null,
"title": "Body plan"
}
|
gradient that acts as a position indicator for cells, turning on other genes, some of which in turn produce other morphogens. A key discovery was the existence of groups of homeobox genes, which function as switches responsible for laying down the basic body plan in animals. The homeobox genes are remarkably conserved between species as diverse as the fruit fly and humans, the basic segmented pattern of the worm or fruit fly being the origin of the segmented spine in humans. The field of animal evolutionary developmental biology ('Evo Devo'), which studies the genetics of morphology in detail, is rapidly expanding with many of the developmental genetic cascades, particularly in the fruit fly Drosophila, catalogued in considerable detail. == See also == == References == == External links == Developmental Biology 8e Online: Patterning of the Mesoderm by Activin Videos The Science of Evolution: Sean B. Carroll explains the genetics of the fruit fly body plan.
|
{
"page_id": 4394717,
"source": null,
"title": "Body plan"
}
|
Neoepitopes are a class of major histocompatibility complex (MHC) bounded peptides. They represent the antigenic determinants of neoantigens. Neoepitopes are recognized by the immune system as targets for T cells and can elicit immune response to cancer. == Description == Epitopes, also referred to as antigenic determinants, are parts of an antigen that are recognized by the immune system. A neoepitope is an epitope the immune system has not encountered before. Therefore it is not subject to tolerance mechanisms of the immune system. As the mutant gene product is only expressed in tumors and is not found in non-cancerous cells, neoepitopes may evoke a vigorous T cell response. Tumor Mutational Burden (TMB, the number of mutations within a targeted genetic region in the cancerous cell's DNA) correlates with the number of neoepitopes, and have been suggested to correlate with patient survival post immunotherapy, although the findings about the neoantigen/immunogenicity association are disputed. Neoepitopes arise from post-translational modifications. The mRNA translates information from the DNA into polypeptide composed of 20 standard amino acids and then proteins. Several of the standard amino acids can be posttranslationally modified by enzymatic processes, or can be altered through spontaneous (nonenzymatic) biochemical reactions. There is increasing evidence that immune recognition of neoepitopes produced by cancer-specific mutations is a key mechanism for the induction of immune-mediated tumor rejection. Opportunities for therapeutic targeting of cancer specific neoepitopes are under investigation. == As target for immunotherapy == Cancer is a patient-specific disease, and no two tumors are alike. Thus, the immunogenicity of each tumor is unique. A novel strategy against cancer is epitope selection for mutanome-directed individualized cancer immunotherapy. Individualized cancer immunotherapy leverages the adaptive immune system by targeting T cells to tumor cells that have a tumor specific mutant antigen (neoantigen) with neoepitopes recognized by a receptor on
|
{
"page_id": 61411039,
"source": null,
"title": "Neoepitope"
}
|
T cells. One challenge is to identify the neoepitopes that trigger a suitable immune response, that is, to find out which neoepitopes in the individual tumor are highly immunogenic. == Cancer vaccines == Individualized cancer immunotherapy includes vaccination with tumor mutation-derived neoepitopes. The concept is based on a mapping of the tumor-specific individual mutanome with identification of a range of suitable neoepitopes for a patient-specific vaccine. It is expected that the neoepitopes in the vaccine will trigger T cell responses to the specific cancer. For the concept of individualized cancer vaccination first data are available. == References ==
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{
"page_id": 61411039,
"source": null,
"title": "Neoepitope"
}
|
The lingual septum consists of a vertical layer of fibrous tissue, extending throughout the entire length of the median plane of the tongue, though not quite reaching the dorsum. The lingual septum is closely associated with the hyoglossus membrane, allowing the binding of the tongue to the hyoid muscles. Visualization through implementing a vertical groove along the tongue called the median sulcus. It is thicker behind than in front, and occasionally contains a small fibrocartilage, about 6 mm. in length. == See also == Tongue piercing Tongue splitting Mouth cavity Tongue Fibrous tissue == References == This article incorporates text in the public domain from page 1132 of the 20th edition of Gray's Anatomy (1918).
|
{
"page_id": 5312225,
"source": null,
"title": "Lingual septum"
}
|
The Debus–Radziszewski imidazole synthesis is a multi-component reaction used for the synthesis of imidazoles from a 1,2-dicarbonyl, an aldehyde, and ammonia or a primary amine. The method is used commercially to produce several imidazoles. The process is an example of a multicomponent reaction. The reaction can be viewed as occurring in two stages. In the first stage, the dicarbonyl and two ammonia molecules condense with the two carbonyl groups to give a diimine: In the second stage, this diimine condenses with the aldehyde: However, the actual reaction mechanism is not certain. This reaction is named after Heinrich Debus and Bronisław Leonard Radziszewski. A modification of this general method, where one equivalent of ammonia is replaced by an amine, affords N-substituted imidazoles in good yields. This reaction has been applied to the synthesis of a range of 1,3-dialkylimidazolium ionic liquids by using various readily available alkylamines. == References ==
|
{
"page_id": 21958369,
"source": null,
"title": "Debus–Radziszewski imidazole synthesis"
}
|
An Isograft is a graft of tissue between two individuals who are genetically identical (i.e. monozygotic twins). Transplant rejection between two such individuals virtually never occurs, making isografts particularly relevant to organ transplantations; patients with organs from their identical twins are incredibly likely to receive the organs favorably and survive. Monozygotic twins have the same major histocompatibility complex, leading to the low instances of tissue rejection by the adaptive immune system. Furthermore, there is virtually no incidence of graft-versus-host disease. In 1993 a research article demonstrated that islet isografts were being transplanted into young diabetic mice [STZ induced diabetic NOD mice] and the mice survived at least about 22 days post transplantation. == References ==
|
{
"page_id": 17239781,
"source": null,
"title": "Isograft"
}
|
The Howland Research Forest is a 555-acre (225 ha) tract of mature evergreen forest in the North Maine Woods, within Penobscot County, central Maine, US. It is located west of the town of Howland. == History == The tract is part of the 1.1 million acres (4,500 km2) of Maine forest sold in 2005 by International Paper (IP) to the Seven Islands Land Company, a private forest investment management holding company. In 2007, the research forest was purchased by Northeast Wilderness Trust ensuring its wild and natural state into the future. The Howland Forest is a founding member of the AmeriFlux and FLUXNET research networks. == Ecology == The Howland Forest study site is located in a boreal transitional forest of the New England/Acadian forests ecoregion. The forest is dominated by mixed spruce, hemlock, aspen, and birch stands ranging in age from 45 to 130 years. The soils are formed on coarse-loamy granitic basal till. == Research forest == The tract had previously been designated as a research forest under IP's ownership, attracting researchers from the US Forest Service, the University of Maine, NASA, NOAA, and the Woods Hole Research Center. Areas of study included acid rain, nutrient cycling, soil ecology, and more recently, forest carbon uptake and loss. The forest has one of the longest records of carbon flux measurement in the world, dating to 1996, providing important information about carbon sequestration in mature forests. == References == == External links == Northeast Wilderness Trust
|
{
"page_id": 11734758,
"source": null,
"title": "Howland Forest"
}
|
The International Society of Biometeorology (ISB) is a professional society for scientists interested in biometeorology, specifically environmental and ecological aspects of the interaction of the atmosphere and biosphere. The organization's stated purpose is: "to provide one international organization for the promotion of interdisciplinary collaboration of meteorologists, physicians, physicists, biologists, climatologists, ecologists and other scientists and to promote the development of Biometeorology". The International Society of Biometeorology was founded in 1956 at UNESCO headquarters in Paris, France, by S. W. Tromp, a Dutch geologist, H. Ungeheuer, a German meteorologist, and several human physiologists of which F. Sargent II of the United States became the first President of the society. ISB affiliated organizations include: the International Association for Urban Climate, the International Society for Agricultural Meteorology, the International Union of Biological Sciences, the World Health Organization, and the World Meteorological Organization. ISB affiliate members include: the American Meteorological Society, the Centre for Renewable Energy Sources, the German Meteorological Society, the Society for the Promotion of Medicine-Meteorological Research e.V., International Society of Medical Hydrology and Climatology, and the UK Met Office. == Publications == ISB publishes the following journals: Bulletin of the Society of Biometeorology International Journal of Biometeorology == References == == External links == Official website
|
{
"page_id": 4132583,
"source": null,
"title": "International Society of Biometeorology"
}
|
Electrometallurgy is a method in metallurgy that uses electrical energy to produce metals by electrolysis. It is usually the last stage in metal production and is therefore preceded by pyrometallurgical or hydrometallurgical operations. The electrolysis can be done on a molten metal oxide (smelt electrolysis) which is used for example to produce aluminium from aluminium oxide via the Hall-Hérault process. Electrolysis can be used as a final refining stage in pyrometallurgical metal production (electrorefining) and it is also used for reduction of a metal from an aqueous metal salt solution produced by hydrometallurgy (electrowinning). == Processes == Electrometallurgy is the field concerned with the processes of metal electrodeposition. There are seven categories of these processes: Electrolysis Electrowinning, the extraction of metal from ores Electrorefining, the purification of metals. Metal powder production by electrodeposition is included in this category, or sometimes electrowinning, or a separate category depending on application. Electroplating, the deposition of a layer of one metal on another Electroforming, the manufacture of, usually thin, metal parts through electroplating Electropolishing, the removal of material from a metallic workpiece Etching, industrially known to Wikipedia as chemical milling == Research trends == === Molten oxide electrolysis === Molten Oxide Electrolysis in steelmaking is utilizing electrons as the reducing agent instead of coke as in conventional blast furnace. For steel production, this method uses an inert anode (Carbon, Platinum, Iridium or Chromium-based alloy) and places iron ore in the cathode. The electrochemical reaction in this Molten Oxide cell can reach up to 1600 °C, a temperature that melts iron ore and electrolyte oxide. Then the molten iron ore decompose following this reaction: Fe2O3(l) + e− → Fe(l) + O2(g) The electrolysis reaction will produce molten pure iron as a main product and oxygen as its by-product. Because this process does not add coke
|
{
"page_id": 4001513,
"source": null,
"title": "Electrometallurgy"
}
|
in the process, no CO2 gas is produced. So no direct greenhouse gas emission. Moreover, if the electricity to run such cells comes from renewable sources, this process may have zero emissions. This technology also can be implemented for producing Nickel, Chromium, and Ferrochromium. Currently the Massachusetts-based Boston Metal company is in a process to scale up this technology to an industrial level. === Direct decarburization electrorefining === The purpose of this method is to reduce carbon content from steel. This process is suitable for secondary steelmaking industry which recycling steel scrap that has variety of carbon content in their feedstock. This method aim to replace current conventional method that utilizing Basic Oxygen Furnace (BOF) to reduce carbon content of iron by blowing oxygen to make it react with carbon and forming CO2. In electrorefining, decarburization process happened in electrochemical cell that composed of inert electrode, slag and steel. During the process, current passing through the cell and made slag and steel melted. Oxygen ion from slag decompose and oxidize carbon on steel and to form CO. That decarburizing reaction occurs in three steps as follows: O−2 + C ⇌ C(O−(ads)) + e− C(O−(ads)) ⇌ C(O(ads)) + e− C(O(ads)) ⇌ CO(g) (ads) = adsorbed intermediate The total reaction from this cell is: C + ½ SiO2 ⇌ CO(g) + ½ Si(l) The SiO2 comes from the slag, based on the reaction above, besides producing CO gas. This method also produces pure silicon (depending on the slag). The benefit of this direct decarburization process is that it does not produce CO2, but rather CO, which is not considered as greenhouse gas. == References ==
|
{
"page_id": 4001513,
"source": null,
"title": "Electrometallurgy"
}
|
A proteolysis targeting chimera (PROTAC) is a molecule that can remove specific unwanted proteins. Rather than acting as a conventional enzyme inhibitor, a PROTAC works by inducing selective intracellular proteolysis. A heterobifunctional molecule with two active domains and a linker, PROTACs consist of two covalently linked protein-binding molecules: one capable of engaging an E3 ubiquitin ligase, and another that binds to a target protein meant for degradation. Recruitment of the E3 ligase to the target protein results in ubiquitination and subsequent degradation of the target protein via the proteasome. Because PROTACs need only to bind their targets with high selectivity (rather than inhibit the target protein's enzymatic activity), there are currently many efforts to retool previously ineffective inhibitor molecules as PROTACs for next-generation drugs. Initially described by Kathleen Sakamoto, Craig Crews and Ray Deshaies in 2001, the PROTAC technology has been applied by a number of drug discovery labs using various E3 ligases, including pVHL, CRBN, Mdm2, beta-TrCP1, DCAF11, DCAF15, DCAF16, RNF114, and c-IAP1. Yale University licensed the PROTAC technology to Arvinas in 2013–14. In 2019, Arvinas put two PROTACs into clinical trials: bavdegalutamide (ARV-110), an androgen receptor degrader, and vepdegestrant (ARV-471), an estrogen receptor degrader. In 2021, Arvinas put a second androgen receptor PROTAC, Luxdegalutamide (ARV-766), into the clinic. == Mechanism of action == PROTACs achieve degradation through "hijacking" the cell's ubiquitin–proteasome system (UPS) by bringing together the target protein and an E3 ligase. First, the E1 activates and conjugates the ubiquitin to the E2. The E2 then forms a complex with the E3 ligase. The E3 ligase targets proteins and covalently attaches the ubiquitin to the protein of interest. Eventually, after a ubiquitin chain is formed, the protein is recognized and degraded by the 26S proteasome. PROTACs take advantage of this cellular system by putting the protein of
|
{
"page_id": 50532084,
"source": null,
"title": "Proteolysis targeting chimera"
}
|
interest in close proximity to the E3 ligase to catalyze degradation. Unlike traditional inhibitors, PROTACs have a catalytic mechanism, with the PROTAC itself being recycled after the target protein is degraded. == Design and development == The protein targeting warhead, E3 ligase, and linker must all be considered for PROTAC development. Formation of a ternary complex between the protein of interest, PROTAC, and E3 ligase may be evaluated to characterize PROTAC activity because it often leads to ubiquitination and subsequent degradation of the targeted protein. A hook effect is commonly observed with high concentrations of PROTACs due to the bifunctional nature of the degrader. Currently, pVHL and CRBN have been used in preclinical trials as E3 ligases. However, there still remains hundreds of E3 ligases to be explored, with some giving the opportunity for cell specificity. Additionally, there have been attempts to produce PROTACs which target bacteria (BacPROTAC) as a way of circumventing antibiotic resistance. These BacPROTACs target the ClpC:ClpP protease system, an analogue with similar function to E3 ubiquitin ligase in bacterial cells. == Benefits == Compared to traditional inhibitors, PROTACs display multiple benefits that make them desirable drug candidates. Due to their catalytic mechanism, PROTACs can be administered at lower doses compared to their inhibitor analogues, though care needs to be taken in achieving oral bioavailability if administered by that route. Some PROTACs have been shown to be more selective than their inhibitor analogues, reducing off-target effects. PROTACs have the ability to target previously undruggable proteins, as they do not need to target catalytic pockets. This also helps prevent mutation-driven drug resistance often found with enzymatic inhibitors. == PROTAC databases == BioGRID is an open public resource containing manually curated molecular interaction data. In addition to its extensive catalogue of genetic and protein interactions, BioGRID also curates chemical
|
{
"page_id": 50532084,
"source": null,
"title": "Proteolysis targeting chimera"
}
|
interactions including experimentally-determined PROTACs and PROTAC-related molecules with accompanying target and E3 information. PROTACpedia, a manually curated and user-contributed PROTAC-specific public access database. E3 Atlas, a comprehensive E3 database that characterizes the potential for specific E3 ligases to be employed for PROTAC design. == References ==
|
{
"page_id": 50532084,
"source": null,
"title": "Proteolysis targeting chimera"
}
|
RepTar is a repository of cellular targets of host and viral miRNAs. == See also == MiRTarBase MESAdb PmiRKB microRNA == References == == External links == http://reptar.ekmd.huji.ac.il.
|
{
"page_id": 31264501,
"source": null,
"title": "RepTar (database)"
}
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Oppenheimer is a 2023 epic biographical drama film written, produced, and directed by Christopher Nolan. It follows the life of J. Robert Oppenheimer, the American theoretical physicist who helped develop the first nuclear weapons during World War II. Based on the 2005 biography American Prometheus by Kai Bird and Martin J. Sherwin, the film dramatizes Oppenheimer's studies, his direction of the Los Alamos Laboratory and his 1954 security hearing. Cillian Murphy stars as Oppenheimer, alongside Robert Downey Jr. as the United States Atomic Energy Commission member Lewis Strauss. The ensemble supporting cast includes Emily Blunt, Matt Damon, Florence Pugh, Josh Hartnett, Casey Affleck, Rami Malek, and Kenneth Branagh. Oppenheimer was announced in September 2021. It was Nolan's first film not distributed by Warner Bros. Pictures since Memento (2000), due to his conflicts regarding the studio's simultaneous theatrical and HBO Max release schedule. Murphy was the first cast member to join, with the rest joining between November 2021 and April 2022. Pre-production began by January 2022, and filming took place from February to May. The cinematographer, Hoyte van Hoytema, used a combination of IMAX 65 mm and 65 mm large-format film, including, for the first time, selected scenes in IMAX black-and-white film photography. As with many of his previous films, Nolan used extensive practical effects, with minimal compositing. Oppenheimer premiered at Le Grand Rex in Paris on July 11, 2023, and was theatrically released in the United States and the United Kingdom on July 21 by Universal Pictures. Its concurrent release with Warner Bros.'s Barbie was the catalyst of the "Barbenheimer" phenomenon, encouraging audiences to see both films as a double feature. Oppenheimer received critical acclaim and grossed $975 million worldwide, becoming the third-highest-grossing film of 2023, the highest-grossing World War II-related film, the highest-grossing biographical film and the second-highest-grossing R-rated
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film of all time at the time of its release. The recipient of many accolades, Oppenheimer was nominated for thirteen awards at the 96th Academy Awards and won seven, including Best Picture, Best Director (Nolan), Best Actor (Murphy), and Best Supporting Actor (Downey). It also won five Golden Globe Awards (including Best Motion Picture – Drama) and seven British Academy Film Awards (including Best Film), and was named one of the top 10 films of 2023 by the National Board of Review and the American Film Institute. == Plot == In 1926, 22-year-old doctoral student J. Robert Oppenheimer grapples with anxiety and homesickness while studying experimental quantum physics under Patrick Blackett at the University of Cambridge in England. Oppenheimer clashes with Blackett, leaving him a poisoned apple, but he later retrieves it. Visiting scientist Niels Bohr advises Oppenheimer to study theoretical physics at the University of Göttingen in Germany. Oppenheimer completes his PhD and meets scientist Isidor Isaac Rabi. They later meet theoretical physicist Werner Heisenberg in Switzerland. Wanting to expand quantum physics research in the United States, Oppenheimer teaches at the University of California, Berkeley and the California Institute of Technology. He marries Katherine "Kitty" Puening, a biologist and ex-communist, and has an intermittent affair with Jean Tatlock, a troubled communist psychiatrist who later dies in an apparent suicide. When nuclear fission is discovered in 1938, after the Germans succeed in splitting the atom, Oppenheimer realizes it can be weaponized. In 1942, during World War II, U.S. Army Colonel Leslie Groves, the director of the Manhattan Project, recruits Oppenheimer as the director of the Los Alamos Laboratory to develop an atomic bomb. Oppenheimer fears the German nuclear research program, led by Heisenberg, might yield a fission bomb for the Nazis sooner. Oppenheimer assembles a team consisting of Rabi, Hans
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Bethe, and Edward Teller, and collaborates with the scientists Enrico Fermi, Leo Szilard, and David L. Hill at the University of Chicago. Teller's calculations reveal an atomic detonation could destroy the world; after consulting with Albert Einstein and having Bethe do his own calculations on the matter, Oppenheimer concludes the chances are "near zero". Teller attempts to leave the project after his proposal to construct a hydrogen bomb is rejected, but Oppenheimer convinces him to stay. After Germany's surrender in 1945, some scientists question the bomb's relevance. Oppenheimer believes it would end the ongoing Pacific War and save lives. The Trinity test is successful, and President Harry S. Truman orders the atomic bombings of Hiroshima and Nagasaki, resulting in Japan's surrender. Though publicly praised, Oppenheimer is guilt-ridden and haunted by the destruction and mass fatalities. After Oppenheimer expresses his remorse to Truman, the president berates him and dismisses his plea to cease further atomic development. As an advisor to the United States Atomic Energy Commission (AEC), Oppenheimer's stance generates controversy, while Teller's hydrogen bomb receives renewed interest amidst the burgeoning Cold War. AEC Chairman Lewis Strauss resents Oppenheimer for publicly dismissing Strauss's concerns about exporting radioactive isotopes and for recommending negotiations with the Soviet Union after the Soviets successfully detonate their own bomb. Strauss also believes that Oppenheimer denigrated him during a conversation Oppenheimer had with Einstein in 1947, though he had in fact expressed his belief that he had caused a chain reaction that would one day destroy the world. In 1954, wanting to eliminate Oppenheimer's political influence, Strauss secretly orchestrates a private security hearing before a Personnel Security Board concerning the renewal of Oppenheimer's Q clearance, during which his loyalty to the United States is questioned. However, the hearing is a kangaroo court. Oppenheimer's past communist ties are
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raised and his associates' testimony is twisted against him, with Teller's being the most damaging. After Kitty vigorously defends herself and her husband, the board no longer suspects Oppenheimer of disloyalty but still revokes his clearance, thereby damaging his public image and limiting his influence on American nuclear policy. In 1959, during Strauss's Senate confirmation hearing for Secretary of Commerce, Hill unexpectedly testifies about Strauss's personal motives for engineering Oppenheimer's downfall. Strauss's nomination is narrowly voted down, enraging him. In 1963, President Lyndon B. Johnson presents Oppenheimer with the Enrico Fermi Award. == Cast == Cillian Murphy as J. Robert Oppenheimer, a theoretical physicist and director of the Los Alamos Laboratory. Emily Blunt as Katherine "Kitty" Oppenheimer, Robert Oppenheimer's wife and a former Communist Party USA member. Matt Damon as Gen. Leslie Groves, a United States Army Corps of Engineers (USACE) officer and director of the Manhattan Project. Robert Downey Jr. as Rear Admiral Lewis Strauss, a retired Naval Reserve officer and high-ranking member of the U.S. Atomic Energy Commission (AEC). Florence Pugh as Jean Tatlock, a psychiatrist, Communist Party USA member, and Robert Oppenheimer's romantic interest. Josh Hartnett as Ernest Lawrence, a Nobel-winning nuclear physicist who worked with Oppenheimer at the University of California, Berkeley. Casey Affleck as Boris Pash, a U.S. Army military intelligence officer and commander of the Alsos Mission. Rami Malek as David L. Hill, a nuclear physicist at the Metallurgical Laboratory, who helped to create the Chicago Pile. Kenneth Branagh as Niels Bohr, a Nobel-winning Danish physicist, philosopher and Oppenheimer's personal idol. Benny Safdie as Edward Teller, a Hungarian theoretical physicist known for being the "father of the hydrogen bomb". Jason Clarke as Roger Robb, an attorney and future U.S. circuit judge who served as special counsel to the AEC at Oppenheimer's security hearing. Dylan
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Arnold as Frank Oppenheimer, Robert's younger brother and a particle physicist who worked on the Manhattan Project. Tom Conti as Albert Einstein, Nobel-winning German theoretical physicist known for developing the theory of relativity. James D'Arcy as Patrick Blackett, Oppenheimer's doctoral supervisor and Nobel-winning physicist at Cambridge University. David Dastmalchian as William L. Borden, a lawyer and executive director of the United States Congressional Joint Committee on Atomic Energy (JCAE). Dane DeHaan as Maj Gen. Kenneth Nichols, a U.S. Army officer and the deputy district engineer of the Manhattan Project. Alden Ehrenreich as a Senate aide to Lewis Strauss during Strauss's nomination for United States Secretary of Commerce. Tony Goldwyn as Gordon Gray, a government official and chairman of the committee deciding the revoking of Oppenheimer security clearance. Jefferson Hall as Haakon Chevalier ("Hoke"), a Berkeley professor who became friends with Oppenheimer at university. Britt Kyle as Barbara Chevalier, Hoke's wife. David Krumholtz as Isidor Isaac Rabi, a Nobel Prize-winning physicist who worked as a consultant on the Manhattan Project. Matthew Modine as Vannevar Bush, head of the Office of Scientific Research and Development. Scott Grimes as Counsel to Lewis Strauss Kurt Koehler as Thomas A. Morgan, an industrialist and former chairman of the board of the Sperry Corporation who was one of the panel members at Oppenheimer's security clearance hearing. John Gowans as Ward V. Evans, a chemist and academic who served as one of the panel members at Oppenheimer's security clearance hearing. Macon Blair as Lloyd K. Garrison, a lawyer who helped to represent Oppenheimer at his security clearance hearing. Gregory Jbara as Sen. Warren Magnuson, Chairman of Senate Commerce Committee. Harry Groener as Sen. Gale W. McGee Tim DeKay as Sen. John Pastore Matthias Schweighöfer as Werner Heisenberg, a German Nobel Prize-winning physicist who worked in Germany's nuclear
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weapons program during World War II. Alex Wolff as Luis Walter Alvarez, a Nobel-winning physicist who worked on the Manhattan Project. Josh Zuckerman as Giovanni Rossi Lomanitz, a physicist who became Oppenheimer's protégé at Berkeley. Rory Keane as Hartland Snyder, a physicist, who collaborated with Oppenheimer to calculate the gravitational collapse of a dust particle sphere. Michael Angarano as Robert Serber, a physicist who worked on the Manhattan Project. Emma Dumont as Jackie Oppenheimer, Frank's wife and Robert's sister-in-law. Guy Burnet as George C. Eltenton, a chemical engineer in the U.S. with ties to the Soviet Union. Louise Lombard as Ruth Tolman, a psychologist close to Oppenheimer during the development of the atomic bomb. Tom Jenkins as Richard C. Tolman, Ruth's husband and General Groves' chief scientific adviser on the Manhattan Project. Olli Haaskivi as Edward Condon, a nuclear physicist who helped with the development of radar and briefly took part in the Manhattan Project. David Rysdahl as Donald Hornig, a chemist who worked on the firing unit at Los Alamos. Josh Peck as Kenneth Bainbridge, a physicist who was the director of the Manhattan Project's Trinity nuclear test. Jack Quaid as Richard Feynman, an American Nobel-winning theoretical physicist who worked in the Theoretical Division at Los Alamos. Gustaf Skarsgård as Hans Bethe, a German-American Nobel-winning theoretical physicist and the head of the Theoretical Division at Los Alamos. James Urbaniak as Kurt Gödel, an Austrian logician and mathematician known for his theorems that revolutionized mathematics and had far-reaching implications for philosophy and computer science. Trond Fausa as George Kistiakowsky, a Harvard professor who took part in the Manhattan Project. Devon Bostick as Seth Neddermeyer, a physicist who discovered the muon and advocated for the implosion-type nuclear weapon used in the Trinity Test. Danny Deferrari as Enrico Fermi, an Italian Nobel-winning
|
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physicist and creator of the Chicago Pile. Christopher Denham as Klaus Fuchs, a German-born physicist who worked on the Manhattan Project and spied for the Soviet Union. Jessica Erin Martin as Charlotte Serber, head technical librarian at Los Alamos. Ronald Auguste as J. Ernest Wilkins Jr., an African American nuclear scientist, mechanical engineer and mathematician who worked with Oppenheimer on the Manhattan Project. Máté Haumann as Leo Szilard, a Hungarian physicist who conceived the idea of nuclear chain reaction in 1933, and later in July 1945 at the Chicago branch of the Manhattan Project circulated the petition to President Truman against unannounced use of atomic weapons on Japan. Olivia Thirlby as Lilli Hornig, a Czech-American scientist who worked on the Manhattan Project. Jack Cutmore-Scott as Lyall Johnson, a security officer at Berkeley who worked at the Manhattan Project. Harrison Gilbertson as Philip Morrison, a physics professor who worked on the Manhattan Project. James Remar as Henry L. Stimson, Secretary of War under President Truman. Will Roberts as George C. Marshall, the United States Army Chief of Staff from 1939 to 1945. Pat Skipper as James F. Byrnes, U.S. Secretary of State and future Governor of South Carolina. Gary Oldman as Harry S. Truman, the 33rd President of the United States who made the decision to drop the two atomic bombs on Hiroshima and Nagasaki in August 1945. Hap Lawrence as Lyndon B. Johnson, the 36th President of the United States. Troy Bronson as Joseph W. Kennedy, a chemist instrumental on the discovery of plutonium, and head of the Chemistry Department at Los Alamos. == Production == === Development === Director Sam Mendes was interested in adapting the 2005 J. Robert Oppenheimer biography American Prometheus by Kai Bird and Martin J. Sherwin. After that project failed to materialize, the book was
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optioned by various filmmakers over the next fifteen years. The authors became pessimistic about a film adaptation. Oliver Stone declined an opportunity to direct, saying "I couldn't find my way to its essence". In 2015, J. David Wargo optioned the book, then commissioned and rejected several scripts. During the COVID-19 pandemic, Wargo flew to Hollywood to meet with actor James Woods, who set up a meeting with Charles Roven, a producer for various Christopher Nolan films, and in turn, Roven gave a copy of the book to Nolan. Both Wargo and Woods are executive producers of the film. Woods said he was asked not to promote the film because his outspoken political views posed a risk to the film's commercial success and awards campaign. Nolan had long desired to make a film about Oppenheimer, even prior to reading American Prometheus. In 2019, towards the end of production on Nolan's science-fiction film Tenet (2020), star Robert Pattinson gave him a book of Oppenheimer's speeches. According to Nolan, the speeches showed Oppenheimer "wrestling with the implications ... of what's happened and what [he's] done". Nolan wanted to depict "what it would have been like to be Oppenheimer in those moments", in contrast to Tenet, which employs time travel to curb a potential weapon of mass destruction. In December 2020, Warner Bros. Pictures announced plans to give its 2021 films simultaneous releases in theaters and on HBO Max, citing the impact of the COVID-19 pandemic on the film industry. Nolan, who had partnered with Warner Bros. on each of his films since Insomnia (2002), was outraged, as he was a staunch supporter of traditional film exhibition. In January 2021, media reports mentioned the possibility that Nolan's next film could be the first not to be financed or distributed by Warner Bros. By mid-2021,
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Nolan had left Warner Bros. and was meeting with other studios to develop his new project. Nolan had previously supported Warner Bros.' decision to give Wonder Woman 1984 (2020) a simultaneous release, saying he felt that situation had been handled properly, but said he had been excluded from any discussions regarding the postponed release of Tenet. In September 2021, it was announced that Nolan would write and direct a biographical film about Oppenheimer and his contributions to the Manhattan Project, with Cillian Murphy in negotiations to star. Due to his strained relationship with Warner Bros., Nolan approached multiple studios, including Sony, Universal, Paramount, and Apple. According to insiders, Paramount was ruled out early in the process due to the replacement of the CEO and chairman, Jim Gianopulos, with Brian Robbins, an advocate for increased streaming-service releases. Nolan signed with Universal because he had previously worked with Donna Langley, chairwoman and chief content officer of the NBCUniversal studio group, on an unsuccessful attempt to make a film version of the UK television series The Prisoner. Langley agreed with Nolan's stance on traditional film exhibition and Universal agreed to finance and distribute Oppenheimer, with production set to begin in the first quarter of 2022. Universal also agreed to Nolan's terms, which included a production budget of $100 million, an equal marketing budget, an exclusive theatrical window ranging from 90 to 120 days, 20 percent of the film's first-dollar gross, and a three-week period both before and after the opening, in which Universal could not release another new film. === Writing === Nolan became aware of Oppenheimer as a youth, after hearing the lyric "How can I save my little boy from Oppenheimer's deadly toy?" in the Sting song "Russians" (1985). He was also inspired by his fears of nuclear holocaust throughout childhood,
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as he lived during the era of Campaign for Nuclear Disarmament (CND) and the anti-nuclear protests in RAF Greenham Common. He felt that "while our relationship with that [nuclear] fear has ebbed and flowed with time, the threat itself never actually went away", and felt the 2022 Russian invasion of Ukraine had caused a resurgence of nuclear anxiety. Nolan had also penned a script for a biopic of Howard Hughes approximately during the time of production of Martin Scorsese's The Aviator (2004), which had given him insight on how to write a script regarding a person's life. Emily Blunt described the Oppenheimer script as "emotional" and remarked that Nolan had "Trojan-Horsed a biopic into a thriller". By September 2021, both Roven and Nolan had begun contacting Bird and Sherwin to discuss the script. During Bird's first meeting with Nolan, he had already written a spec script while they discussed the script's content, although Nolan did not disclose the script to them yet. Oppenheimer is the first screenplay written by Nolan in the first person, as he wanted the narrative to be conveyed from Oppenheimer's perspective. He described the "texture" of the film being "how the personal interacts with the historic and the geopolitical" with the intention of making it a cautionary tale. He began developing the script after he completed Tenet and wrote it in only a few months; he had already been thinking about making a film about Oppenheimer for over 20 years. A major plot element is Oppenheimer's response to the long-term consequences of his actions. Nolan wished to explore the phenomenon of delayed reactions, as he felt people are not "necessarily confronted with the strongest or worst elements of [their actions] in the moment". He also chose to alternate between scenes in color and black-and-white to convey
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the story from both subjective and objective perspectives, respectively, with most of Oppenheimer's view shown via the former, while the latter depicts a "more objective view of his story from a different character's point of view". Wanting to make the film as subjective as possible, the production team decided to include visions of Oppenheimer's conceptions of the quantum world and waves of energy. Nolan noted that while Oppenheimer never publicly apologized for his role in the atomic bombings of Hiroshima and Nagasaki, he still believed Oppenheimer had felt genuine guilt for his actions and thus portrayed him as exhibiting those feelings. Nolan began by trying to find the "thread that connected the quantum realm, the vibration of energy, and Oppenheimer's own personal journey" and sought to portray the difficulties in his life, particularly regarding his sex life. As such, Nolan wanted to candidly portray his affair with Jean Tatlock. He also wanted to explore Tatlock's influence on Oppenheimer's life, since she was a Communist, which had "enormous ramifications for [Oppenheimer's] later life and his ultimate fate". Nolan also sought to explore the relationship between Oppenheimer and Admiral Lewis Strauss, former chair of the U.S. Atomic Energy Commission, having been inspired by the relationship between Wolfgang Amadeus Mozart and Antonio Salieri as depicted in Amadeus (1984). Another critical moment of the film was the meeting in which President Harry S. Truman called Oppenheimer a "crybaby". Nolan wanted to convey the scene from Oppenheimer's perspective and felt it was a "massive moment of disillusion, a huge turning point [for Oppenheimer] in his approach to trying to deal with the consequences of what he'd been involved with", while also underscoring that it is a "huge shift in perception about the reality of Oppenheimer's perception". He wanted to execute a quick tonal shift after
|
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the atomic bombings of Hiroshima and Nagasaki, desiring to go from the "highest triumphalism, the highest high, to the lowest low in the shortest amount of screen time possible". For the ending, Nolan chose to make it intentionally vague to be open to interpretation and refrained from being didactic or conveying specific messages in his work. However, he did have the intention to present a "strong set of troubling reverberations at the end". === Casting === Oppenheimer marks the sixth collaboration between Nolan and Cillian Murphy, and the first starring Murphy as the lead. To prepare for the role, Murphy read extensively on Oppenheimer's life and was inspired by David Bowie's appearance in the 1970s. Nolan called Murphy one day to ask him to play the part, and Murphy enthusiastically accepted, excited to play a lead role in a Nolan film. Afterward, Nolan flew to Dublin to meet with Murphy, who read the script in Nolan's hotel room. Murphy lost an undisclosed amount of weight for the role in order to better match the real-life Oppenheimer's gaunt appearance. Nolan also set up a phone call between Murphy and Nobel laureate Kip Thorne, who had previously worked with Nolan on Interstellar (2014). As a graduate student, Thorne had attended some of Oppenheimer's seminars, and explained to Murphy his experience with Oppenheimer's gift for facilitating group discussions of difficult scientific concepts. The casting process was so secretive that some cast members did not know which role they would be playing until they signed on. Robert Downey Jr., Matt Damon, and Emily Blunt took pay cuts to work on the film, with each earning $4 million in lieu of their usual $10–20 million upfront salary. Downey went to Nolan's house to read the script, which was printed in black on red paper. Downey
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would later describe Oppenheimer as "the best film" in which he has appeared to date. Downey previously met with Nolan for the role of Jonathan Crane / Scarecrow in Batman Begins (2005), but Nolan felt Downey wasn't right for the role, which went to Murphy. Blunt met Nolan in Los Angeles and, when she was offered the role of Katherine "Kitty" Oppenheimer, she enthusiastically accepted; she also contacted Murphy to get an expectation of what working with Nolan would be like. Asked to play the part of Leslie Groves, Damon—who had appeared in Nolan's Interstellar—was taking a break from acting as a result of negotiations with his wife Luciana Bozán Barroso in couples therapy, but signed on to Oppenheimer as he had reserved one exception: if Nolan offered him a role in a film. Nolan cast writer-director Benny Safdie as physicist Edward Teller after asking director Paul Thomas Anderson about his experience directing Safdie in Licorice Pizza (2021). Safdie had worked alongside a nuclear physicist at Columbia University while in high school. It is Nolan's first film since Insomnia (2002) to not feature Michael Caine. Glen Powell auditioned and was rejected for the role that went to Josh Hartnett. For Harry S. Truman's appearance, Nolan sought his collaborator Gary Oldman, who was on a break from filming the Apple TV+ series Slow Horses (2022–present); Oldman told Nolan that he was contractually obliged to not cut his hair, so either he could play Truman with a prosthetic cap and a wig or get someone else to play the part, which Nolan agreed. === Filming === Pre-production had begun by January 2022 in New Mexico, where a two-day casting call took place in Santa Fe and Los Alamos for people to audition to play local residents, military personnel, and scientists. Another casting
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call was held in February. Principal photography began on February 28, 2022, at Ghost Ranch in New Mexico, and lasted for 57 days with Hoyte van Hoytema serving as cinematographer. The original shooting schedule had set aside approximately 85 days for filming. However, during pre-production, it had become clear that principal photography could not be completed within $100 million over that many days on location all over the United States. To efficiently use the budget for location shooting in California and New Jersey and constructing high-quality historically accurate sets in New Mexico, Nolan compressed the shooting schedule from 85 to 57 days. Murphy, who appears in nearly every scene, described the pace as "insane". Oldman said he would be on set for a day in May for "one scene, a page and a half". The original choice for Oval Office location in the Nixon Presidential Library fell through a week before filming, and since Oldman's dates were unmovable, the production design team redressed the Oval Office set from the HBO series Veep (2012–2019), which according to Ruth De Jong had fallen into "nightmarish" disrepair. Nolan filmed his eldest child, his daughter Flora, in a scene in which she played a young woman disintegrated in a nuclear explosion. It appears in the film as one of Oppenheimer's visions, in which Nolan intended to show "that if you create the ultimate destructive power, it will also destroy those who are near and dear to you". The film used a combination of IMAX 65 mm and 65 mm large-format film. It is also the first film to shoot sections on IMAX black-and-white photographic film, which Kodak created and FotoKem developed specifically for the film. Van Hoytema used 50 mm and 80 mm Hasselblad lenses when filming on the IMAX MKIV or IMAX MSM
|
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9802 cameras, while scenes shot on the Panavision Panaflex System 65 Studio cameras were shot using Panavision Sphero 65 and Panavision System 65 lenses. Additionally, the production had Panavision construct a custom probe lens to allow the filmmakers to use IMAX cameras for macro photography and microphotography to record the miniature effects. Miniatures were filmed with IMAX cameras at 48 frames per second, while miniatures needing higher speed were shot on Super 35 mm film with an Arriflex 435 ES camera at 150 frames per second. In the second week of April, filming took place on location at the Institute for Advanced Study in Princeton, New Jersey. Filming also occurred in California, primarily around the campus of the University of California, Berkeley. Scenes set in the city of Berkeley itself were filmed in Pasadena. During a 2021 research trip, Nolan discovered that Los Alamos had drastically changed from its 1940s appearance and could not be used for exterior shots of the town; for example, the town's equivalent of a Main Street has a Starbucks. Instead, the production team constructed a version of 1940s-era Los Alamos on top of a similar plateau at Ghost Ranch. It took three months to build the set, which was used for only six shooting days. The general plan was to shoot only exterior shots on the set at Ghost Ranch, then shoot interior shots on location inside various historic buildings in the real town of Los Alamos. Interior shooting in Los Alamos began on March 8, 2022. Many scenes in the film take place in academic lecture halls; to save time and money, the production team decided against attempting to reconstruct those halls as sets at Ghost Ranch, and shot them inside a historic Women's Army Corps dormitory in Los Alamos. Scenes were also filmed
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in Oppenheimer's original cabin in Los Alamos, which had been restored. Kai Bird visited the set and was impressed by Murphy's performance. The New York hotel scenes were shot in Albuquerque's Old Post Office building, while the Washington, D.C. scenes were shot in state government buildings in the state capital of Santa Fe. Although the news coverage surrounding the film's release implied that most of the film was shot in New Mexico, the official making-of book Unleashing Oppenheimer revealed that many of the film's most important scenes were shot within the studio zone in Los Angeles County. Early on, three days were set aside for filming at UCLA's Kerckhoff Hall, which was used for both the Cambridge and Göttingen scenes. The Millennium Biltmore Hotel in Downtown Los Angeles stood in for the Mark Hopkins Hotel for one of Oppenheimer's encounters with Tatlock, for the Plaza Hotel for Strauss's 1949 birthday celebration, and for an unnamed Washington, D.C. hotel for the scene where Szilard and Hill try to get Oppenheimer to sign a petition against dropping the bomb on Japan. Oppenheimer's security hearing was shot in Alhambra, California, in a "disused office building in the former manufacturing headquarters for the petrochemical company C.F. Braun & Co." The scene in which Oppenheimer's security clearance was revoked was shot on May 19, 2022, the production's last day in Alhambra. Filming involved the use of real explosives to recreate the Trinity nuclear test, forgoing the use of computer-generated graphics. When this news first broke online, many fans (aware of Nolan's famous preference for in-camera practical effects) thought it meant he had set off a real atomic bomb. Nolan later remarked that it was both "flattering" and "scary" that his fans would think that of him. The production team was able to obtain government permission
|
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to film at White Sands Missile Range, but only at highly inconvenient hours, and therefore chose to film the scene elsewhere in the New Mexico desert. The production filmed the Trinity test scenes in Belen, New Mexico, with Murphy climbing a 100-foot steel tower, a replica of the original site used in the Manhattan Project, in rough weather. A special set was built in which gasoline, propane, aluminum powder, and magnesium were used to create the explosive effect. Although they used miniatures for the practical effect, the special effects supervisor, Scott R. Fisher, referred to them as "big-atures", since the special effects team had tried to build the models as physically large as possible. To make the models look closer to their intended real-life size, the team used forced perspective. Visualizations of the interactions between atoms, molecules and energy waves, as well as the depiction of stars, black holes and supernovas, were also achieved through practical methods. Nolan claimed the film contains no computer-generated effects, and used practical effects to achieve "real-world imagery". The last portion of principal photography was for Nolan and van Hoytema to travel to Europe to obtain establishing shots for the early European phase of Oppenheimer's life. For example, they did not bother with shooting in any actual part of the University of Cambridge; "van Hoytema simply set up a camera across the river". Filming wrapped in May 2022. === Post-production === Editing was completed by Jennifer Lame, who had previously edited Tenet. While inspecting the footage during editing, Nolan and Lame performed "character passes" to ensure all the characters were properly displayed on screen, due to the film having a faster pace than most traditional blockbusters. Visual effects were handled by DNEG, which produced more than 100 VFX shots from more than 400 practically shot
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elements, marking their eighth collaboration with Nolan. Andrew Jackson was the visual effects supervisor, who stated that the film used mostly "invisible" visual effects through "'in-camera' special effects created on set". Digital compositing was used for the Trinity scene to add multi-layers to the explosion which was shot in a multifaceted viewpoint. There were 160 VFX artists who worked on the film, 134 of whom were left uncredited. Steven Spielberg was the first person to see the final cut, in a private screening of its first 70mm print. Nolan said: "He said some very kind things, but really just to watch him watch ... I wasn't even supposed to watch it with him, but seeing the great master watching? It was sort of irresistible." == Music == Ludwig Göransson composed the score for the film, after doing so for Nolan's previous film, Tenet. Göransson's score was featured in a trailer for the film on May 8, 2023. It was also featured in the Universal Pictures exclusive five-minute Opening Look on July 13. Nolan had advised him to use a solo violin for Oppenheimer's central theme in the film, with Göransson remarking that he had felt that it could go from "the most romantic, beautiful tone in a split second to neurotic and heart wrenching, horror sounds". == Marketing == Oppenheimer's teaser trailer was released on July 28, 2022, featuring a live countdown to 5:29 a.m. (MDT) on July 16, 2023, the 78th anniversary of the first detonation of an atomic weapon; it premiered in screenings of Nope before being posted online on Universal's social media profiles. Empire commented that it is exemplary of Nolan's style: "heady, brooding stuff with a real sense of weight". In December 2022, two trailers premiered in front of Avatar: The Way of Water, with one
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being exclusive to IMAX theaters and the other being shown in all other formats. The latter was eventually released online. In May 2023, an official main trailer debuted during preview screenings of Guardians of the Galaxy Vol. 3. It was subsequently released to the public on May 8, 2023, alongside a theatrical release poster. == Release == === Theatrical === Oppenheimer had its world premiere at Le Grand Rex in Paris on July 11, 2023, followed by the British premiere at Odeon Luxe Leicester Square in London on July 13, and the American premiere at AMC Lincoln Square 13 in New York City on July 17. Both the London and the New York premieres were affected by the SAG-AFTRA strike, as some actors left the London premiere early, and Universal Pictures canceled the red carpet event for the New York premiere. SAG-AFTRA President Fran Drescher later claimed the studios "duped" the guild into accepting a twelve-day-extension for negotiations to continue promoting summer films like Oppenheimer. Oppenheimer was released theatrically on July 21, 2023, by Universal Pictures. In addition to standard digital cinemas, it was also released in various film formats including IMAX 70 mm (30 prints), standard 70 mm (113 prints) and 35 mm (around 80 prints). The film was released on the same day as Barbie, a fantasy comedy film directed by Greta Gerwig based on Mattel's Barbie fashion dolls and media franchise, and distributed by Warner Bros. Many speculated that the decision by Warner Bros. to release Barbie on the same day as Oppenheimer was made in order to deplete ticket sales of Oppenheimer as retaliation for Nolan releasing the film with Universal. Due to the tonal and genre dissonance between the two films, many social media users created memes about how the two films appealed to different
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{
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audiences, and how they should be viewed as a double feature. The trend was dubbed "Barbenheimer", and was described as counterprogramming during a summer of "entertainment industry meltdown". Cillian Murphy had endorsed the phenomenon, saying "My advice would be for people to go see both, on the same day. If they are good films, then that's cinema's gain." In March 2022, Universal Pictures halted the release of its titles in Russia, joining other major American film distributors in the boycott against the country following its invasion of Ukraine in February 2022. Oppenheimer had also been banned by Russia's Ministry of Culture, which had refused to license screenings of the film, stating that it did not meet their goals of "preserving and strengthening traditional Russian spiritual values". The film was not released in Japan until eight months after its initial global release. Variety noted the controversial reputation in Japan due to the atomic bombings of Hiroshima and Nagasaki. A Universal spokesperson said that "plans have not been finalized in all markets". American films are often released in Japan a few months after the initial theatrical release. In December 2023, the independent Japanese film distributor Bitters End announced that it would theatrically release the film in 2024, as Universal's distributor in Japan Toho-Towa opted not to release it. The film was later released by Bitters End in Japan on March 29, and during its first three days, it was ranked as the country's highest grossing foreign film after making 379.3 million yen ($2.5 million) at the box office. ==== Classifications and censorship ==== In the United States, the film received an R-rating from the Motion Picture Association for "some sexuality, nudity, and language". It is Nolan's first film to receive that rating since Insomnia (2002). In Australia, the film received an MA
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{
"page_id": 66850554,
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15+ rating from the Australian Classification Board board for "strong sex and a suicide scene". In the United Kingdom, the film received a 15 certificate from the British Board of Film Classification for "strong language and sex", meaning anyone under the age of 15 cannot be admitted to view the film. In some countries, including those in the Middle East, South Asia and Southeast Asia, Universal distributed a version of the film with Florence Pugh's nude body covered by a computer-generated black dress. In India, Oppenheimer was released with all scenes depicting nudity, sex and cigarette smoking being censored, earning the U/A certificate from the Central Board of Film Certification (CBFC) while retaining the running time. ==== Bhagavad Gita controversy ==== The audio of the scene in which Tatlock directs Oppenheimer to read a verse from the Hindu scripture Bhagavad Gita, "I am become Death, destroyer of worlds", remained intact. As NDTV reported, the Minister for Information and Broadcasting Anurag Thakur questioned how the CBFC certified the film with the verse heard during such circumstance in the first place, and asked the scene to be deleted. Hindu nationalists were angered by the scene and demanded its removal. Among them was journalist Uday Mahurkar, who wrote an open letter to Nolan calling the scene a "direct assault on religious beliefs of a billion tolerant Hindus", and demanded its removal from all releases of Oppenheimer across the world. On the other hand, actor Nitish Bharadwaj told The Times of India that "The use of this verse in the film should also be understood from Oppenheimer's emotional state of mind. A scientist thinks of his creation 24x7x365 days, irrespective of what he is doing. His mind space is consumed fully of his creation & the physical act is just a natural mechanical act."
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{
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=== Home media === Oppenheimer was released on Ultra HD Blu-ray, regular Blu-ray and DVD formats including digital on November 21, 2023. As the former two releases sold out days after release, Universal worked on restocking before the holiday season. Nolan was vocal during the home release campaign of the film about the importance of physical media libraries, stating that letting films only exist digitally or on streaming services allows companies to have too much control and creates a danger for film preservation. The film was released for streaming in the United States exclusively on Peacock and in Canada on Amazon Prime Video on February 16, 2024. Additionally, it began streaming on Jio Cinema in India from March 21, 2024. == Reception == === Box office === Oppenheimer grossed $330.1 million in the United States and Canada and $645.7 million in other territories, for a worldwide total of $975.8 million; $190 million of which came from IMAX alone. It is the third-highest-grossing R-rated film of all time behind Joker (2019) and Deadpool & Wolverine (2024). In September 2023, Oppenheimer became the highest-grossing biographical film of all time, surpassing Bohemian Rhapsody (2018). By August 2023, Oppenheimer had become the highest-grossing film ever to not reach the top spot at the domestic box office, although in its sixth weekend it topped the worldwide box office with a total of $38.12 million, surpassing Barbie for the first time. It is also the highest grossing World War II-related film, surpassing Dunkirk (2017), also a Nolan film. Additionally, Oppenheimer became one of the top five highest-grossing IMAX releases, earning $183 million (approximately 20% of its total gross), over $17 million of which was earned from the 30 screens showing IMAX 70 mm prints. The film was booked to be rereleased in IMAX theaters on November
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{
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3, including six IMAX 70 mm prints, as these theaters reported selling out during the initial release. Deadline Hollywood calculated the net profit of the film to be $201.9 million, when factoring together all expenses and revenues. ==== United States and Canada ==== In the United States and Canada, Oppenheimer was released alongside Barbie, in what became known as 'Barbenheimer'. The week of their releases, AMC Theatres announced that over 40,000 AMC Stubs members had already pre-booked tickets to both films on the same day. After grossing $33 million on its first day (including $10.5 million from Thursday night previews), it went on to debut to $82.5 million, finishing second behind Barbie and marking one of the best opening weekends ever for an R-rated drama. 64% of the audience was male, with 33% being 18–34 years old. The Barbenheimer phenomenon was credited with boosting interest in the film, with a total of 79% of tickets sold over the weekend being for the two films (27% for Oppenheimer), a combined total of 18.5 million people. The opening weekend was Nolan's best for an original film, being the highest of his filmography outside of the latter two films from The Dark Knight trilogy. It achieved the third-highest opening weekend for a biopic film, behind The Passion of the Christ (2004) and American Sniper (2014). Oppenheimer made $46.2 million in its second weekend (a drop of 44%), remaining in second behind Barbie. The film made $28.7 million in its third weekend, finishing third behind Barbie and newcomer Meg 2: The Trench. On August 16, Oppenheimer surpassed Sing (2016) to become the highest-grossing film to never reach the number one spot at the box office. During its fourth weekend, the film made $18.8 million (a drop of 35%) rising back up to second place.
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In its fifth and sixth weekends, the film grossed $10.7 million and $9 million (a drop of 43% and 16% respectively), finishing in third and fourth place at the box office and passing $300 million domestically in its sixth weekend. Following its 13 Oscar nominations, the film expanded from 1,008 theaters to 2,262 in its 28th week of release and made $1 million, an increase of 284% from the previous weekend. ==== Japan ==== In Japan, Oppenheimer was released on March 29, 2024. Prior to its release, it attracted controversy there, and Warner Bros. issued an apology following criticism of the Barbenheimer phenomenon as insensitive. Despite the outcry, the film would do very well in Japan, grossing $2.5 million and placing third in the country's box office during its opening weekend. The film received a range of comments from the Japanese public. Some theaters displayed content warnings for the film. A number of people from Hiroshima who viewed the film reported feeling discomfort and distress while watching it. One point of contention was on the choice to not visually depict the nuclear bombing of Japan. A number of Japanese people praised the choice and others felt that it resulted in the downplaying or glorification of the bombing. Takashi Hiraoka, former mayor of Hiroshima, reportedly felt that the horror of nuclear weapons had not been sufficiently portrayed in the film. A number of people reported feeling that Oppenheimer was glorified in the film for his role in developing the bomb, and a number of people felt that he was also a victim of his circumstances and experienced distress from it. Masao Tomonaga, who experienced one of the nuclear bombings, felt that the film was "anti-nuclear" and expressed disappointment in the lack of a scene for the atomic bombing in Japan, but
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{
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was reportedly satisfied with the portrayal of Oppenheimer's distress after the bombings. A Hiroshima resident was reported advocating for more people to see the film, and another advocated for fewer. When commenting on Oppenheimer's success in the country, USC School of Cinematic Arts' Vice Dean of Faculty, Akira Mizuta Lippit, stated in an article for Deadline Hollywood in May 2024, "Previous films about Japan, good and bad, some offensive or ignorant, have nonetheless enjoyed box office success in Japan," noting how films like Pearl Harbor and The Last Samurai were "embraced by Japanese audiences," whereas other films like Memoirs of a Geisha were "a little less so." ==== Other territories ==== Outside the United States and Canada, Oppenheimer grossed $98 million in its opening weekend. The following weekend, it earned $77.1 million, dropping by 21% to become Nolan's highest-grossing film in 30 countries, including India, Saudi Arabia, United Arab Emirates and Turkey. In its third weekend, Oppenheimer grossed $52.8 million (a drop of 31%) and $32 million in its fourth weekend. It held well in the following weeks, making $32 million and $29.1 million in its fifth and sixth weekends. As of September 10, 2023, the highest-grossing territories were the UK ($75 million), China ($61.6 million), Germany ($51.9 million), France ($43.1 million) and Australia ($25.9 million). === Critical response === Oppenheimer received critical acclaim. Critics praised the film primarily for its screenplay, cast performances, and visuals. It was frequently ranked as one of Nolan's best films, and one of the best of 2023, although some criticism was aimed towards the film's pacing (particularly in the second half) and the writing of the female characters. On the review aggregator website Rotten Tomatoes, 93% of 508 critics' reviews are positive, with an average rating of 8.6/10. The website's consensus reads: "Oppenheimer marks
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another engrossing achievement from Christopher Nolan that benefits from Murphy's tour-de-force performance and stunning visuals." Metacritic, which uses a weighted average, assigned the film a score of 90 out of 100, based on 69 critics, indicating "universal acclaim". Audiences polled by CinemaScore gave the film an average grade of "A" on an A+ to F scale, while those polled by PostTrak gave it a 93% overall positive score, with 74% saying they would definitely recommend the film. Richard Roeper of the Chicago Sun-Times gave Oppenheimer a perfect four out of four, describing it as "magnificent" and "one of the best films of the 21st century". The A.V. Club's Matthew Jackson deemed it a "masterpiece", adding that "it's Christopher Nolan's best film so far, a step up to a new level for one of our finest filmmakers and a movie that burns itself into your brain". Empire's Dan Jolin labeled it a "masterfully constructed character study", taking particular note of Murphy's performance and van Hoytema's IMAX cinematography. Peter Suderman, writing for Reason, said that the film leaves the viewer with a sense of "fear and foreboding about the horror of full-on nuclear conflict in the wake of the nuclear bomb. Humanity is both great and terrible. Oppenheimer isn't just a movie—it's a warning." Matt Zoller Seitz, writing for RogerEbert.com, awarded Oppenheimer a full four out of four rating. He lauded Nolan's storytelling, exploration of Oppenheimer's character and its technical achievements, concluding: "As a physical experience, Oppenheimer is something else entirely—it's hard to say exactly what and that's what's so fascinating about it". He also compared the role of the conversation between Oppenheimer and Einstein in the film to the role of "Rosebud" in Citizen Kane. Peter Travers described the film as a "monumental achievement" and "one of the best films you'll
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{
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"source": null,
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see anywhere". Caryn James of BBC Culture similarly termed it "boldly imaginative and [Nolan's] most mature work yet", adding that it combined the "explosive, commercially-enticing action of The Dark Knight trilogy" with the "cerebral underpinnings" of Memento, Inception and Tenet. IGN critic Siddhant Adlakha ranked Oppenheimer 10/10, describing it as "a three-hour biopic that plays like a jolting thriller" and Nolan's most "abstract" work yet. Despite praising the film's themes and performances, CNN's Brian Lowry believed that "Nolan juggles a lot, in a way that somewhat works to the movie's detriment". Owen Gleiberman of Variety found the film's first half "mesmerizing" and "tick[ing] with cosmic suspense", but wrote that "a certain humming intensity leaks out of the movie" after the Trinity Test sequence, which was itself described as a "letdown". Manohla Dargis of The New York Times called the film "a brilliant achievement in formal and conceptual terms", praising Nolan for capturing "the kinetic excitement of intellectual discourse" and comparing the film's complex narrative structure to a "Cubistic portrait". However, she found some of the cameos by supporting actors such as Malek "distracting", and noted that the film's black-and-white scenes could feel "overlong" despite ultimately working in service of Nolan's narrative intentions. In a mixed review, Odie Henderson of The Boston Globe called the film "visually stunning but emotionally empty", criticizing Nolan's screenplay for rendering Oppenheimer an "enigma whose inner life is expressed by gimmicky cuts to scenes of outer space rather than evidence of human emotions." Furthermore, Henderson negatively characterized the film's second half as "an interminable series of scenes set in courtrooms and at congressional hearings", and felt Pugh and Blunt were "wasted" in "severely underwritten" roles. While praising how the film acknowledges the contribution of "American scientists and American enterprise", Brett Mason complained that it omits the
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{
"page_id": 66850554,
"source": null,
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crucial contributions of non-Americans who ensured the work was able to commence as early as December 1941: "Nolan completely ignores the crucial role that British science and Australian physicist Mark Oliphant played in jump-starting the quest." Writing for the Los Angeles Times, Justin Chang defended Nolan's accurate depiction of how Oppenheimer could not see the true victims of his work. Chang wrote that instead of satisfying "representational completists" by detouring to Hiroshima and Nagasaki, "Nolan treats them instead as a profound absence, an indictment by silence". Chang later won the 2024 Pulitzer Prize for Criticism for that article. Richard Brody of The New Yorker described the film as a "History Channel movie with fancy editing" and wrote, "I was tempted to call it a movie-length Wikipedia article. But after a look online, I realized I was giving Wikipedia too little credit—or Christopher Nolan, the movie's writer and director, too much". For IndieWire's annual critics poll, in which 158 critics and journalists from around the world voted, Oppenheimer was placed second in their Best Film list, with 69 overall mentions and 17 first-place votes. Nolan was also ranked second on the Best Director list, while his screenplay was placed eighth. Murphy was the highest-placed actor on the Best Performance list (fourth overall) while Van Hoytema's work topped the Best Cinematography list. Oppenheimer also appeared in over 410 critics' lists of the best films released in 2023, and was ranked first in 99 of them. The film garnered significant praise from prominent filmmakers. Oliver Stone deemed the film "a classic, which I never believed could be made in this climate". Paul Schrader called Oppenheimer, "the best, most important film of this century", while Denis Villeneuve called it "a masterpiece". Steven Soderbergh said of the film, "Oppenheimer is a real accomplishment. I read
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{
"page_id": 66850554,
"source": null,
"title": "Oppenheimer (film)"
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somewhere that Chris [Nolan] implied that this is the movie he's been building toward, and I think he's right. And I'm thrilled that it's a massive hit." Spike Lee also praised the film, calling it a "great film", but felt that it should have shown what happened to the Japanese people, given the film's length. Japanese director Takashi Yamazaki said, "As a person of Japanese ancestry and descent, my response to Oppenheimer [is that] I would like to dedicate a different film to that when that day comes." Other filmmakers, including A. V. Rockwell, Joe Dante, Reinaldo Marcus Green, Chad Hartigan, Max Hechtman, Don Hertzfeldt, Matt Johnson, Raine Allen-Miller, James Ponsoldt and Adam Wingard cited it as among their favorite films of 2023. Korean film critic Yim Jeong-sik said "Oppenheimer depicts the tragedy of the combination of science and politics. Oppenheimer developed the atomic bomb to stop the Nazis from developing nuclear weapons, but the result was the bomb dropped on Japan and countless casualties. The film coldly shows how science loses its purity and becomes a tool of the state through the process of Oppenheimer's choice combining with America's imperial ambitions." In August 2023, Oppenheimer ranked number three on Collider's list of "The 20 Best Drama Movies of the 2020s So Far," with the site writing that Nolan "explores the world's obsession with destructive nuclear weapons from the perspective of their creator; using the Greek myth of Dante [sic] as an inspiration, Oppenheimer makes it clear that once this type of power is unleashed, it is bound to be used again." In March 2025, the film ranked number two on Comic Book Resources' list of "10 Great Dramas From the 2020s That Are Already Instant Classics," with Dante Santella writing "Loaded with relevant themes that pertain to global policy,
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{
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"source": null,
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the film is not only a great dramatic tale but also a prophetic warning. Whether enjoyed as entertainment or analyzed for its subject matter, Oppenheimer is the rare kind of movie that can be appreciated over time, thereby keeping the film’s classical legacy intact for fans." The New York Times also listed the film as among "The Movies We've Loved Since 2000." === Influence on legislation === The renewed attention to the Trinity site and associated nuclear testing encouraged the United States Congress to revise the Radiation Exposure Compensation Act (1990), which provided compensation programs for people affected by radiation and nuclear testing during the Cold War, known as "Downwinders" and primarily consisting of the Navajo Nation. The United States Senate approved amendments to accommodate additional services to people in New Mexico, but it has not passed through Congress as the House of Representatives had not yet debated its inclusion as part of the national defense bill for the 2024 fiscal year. As of March 2025, there have been continuous efforts to revive and expand the RECA. New Mexico lawmakers expressed, in a non-binding resolution (House Memorial 15), their support for federal legislation to expand compensation for individuals affected by radiation exposure, particularly those involved with uranium mining and Downwinders who were affected by the Trinity test and other related nuclear activities. == Accuracy and omissions == Some scenes in the movie were taken word-for-word out of the book or real life events. Many of the changes are small embellishments or changes from real life. For example, Oppenheimer was not as excited about his discovery of black holes as shown in the film since he did not know how significant it would become. The study was indeed released on the same day Germany invaded Poland, as shown in the film.
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{
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"source": null,
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During the Trinity test, Donald Hornig had his hand on the kill switch for a faster reaction time and not near it as depicted in the film. Truman did call Oppenheimer a "crybaby" but in a letter to Dean Acheson one year later, not immediately after meeting Oppenheimer. It was also pointed out that the incorrect American flag was used. In the film, the current 50-star flag is shown. This version was not adopted until 1960. During the war, the American flag had only 48 stars as Hawaii and Alaska had yet to become states. The scene where Oppenheimer poisons his tutor's apple at university is based on accounts that Oppenheimer gave of the incident, but it is unclear whether it occurred in real life. Oppenheimer is depicted as putting potassium cyanide in the apple before having a change of heart the next day and narrowly preventing it from being eaten. There is no evidence that Niels Bohr nearly ate the apple or had any involvement in the incident. Oppenheimer and Einstein were friends, but the specific conversations which the film revolves around never happened. Oppenheimer took his concerns about an unstoppable chain reaction to physicist Karl Compton at MIT, not Einstein. Although the film portrays Groves' aggressive recruitment of Oppenheimer, Arthur Compton at the Metallurgical Laboratory had earlier recruited and appointed Oppenheimer to take over the research into the bomb-design part of what became the Manhattan Project. As Strauss correctly points out in the film's dialogue, Oppenheimer never expressed regret for the atomic bombings, but as Chang explained in his Pulitzer Prize-winning article, the true situation not depicted in the film was that Oppenheimer avoided giving an apology when confronted by a reporter during his 1960 visit to Tokyo and Osaka. In addition to their interpersonal conflicts, Strauss had
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{
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"source": null,
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another reason to undermine Oppenheimer's credibility by revoking his security clearance: Oppenheimer was opposed to further development of the hydrogen bomb by the United States. Scott Sagan describes the loss of Oppenheimer's influence as a possible constraint upon the nuclear arms race between the United States and USSR as a "broader tragedy" less clearly depicted in the film than the scientist's personal tragedy, but he called the production "highly accurate" otherwise for a Hollywood film. Many efforts undertaken at other Manhattan Project sites like Hanford, Washington and Oak Ridge, Tennessee were not shown. Most of them, overseen by General Leslie Groves, focused on understanding and producing the radioactive material that powered the nuclear explosions. In addition to the team at Los Alamos, those working at other Project sites, particularly the University of Chicago's Metallurgical Laboratory, also expressed concerns about using the atomic bomb against Japan. The film was criticised for its omission of the 30 Native American families who were forcibly displaced from Los Alamos in 1942 to make space for the experiment. Another technical problem accurately represented throughout the film was plutonium production. This can be analyzed through the occurrence of discussions of fizzle, ingenuity, engineering breakthroughs and setbacks, and once again, the determination to succeed. The film focused on the great cost it took to obtain the plutonium, as well as the overall process of breeding plutonium. Enrico Fermi, a main scientist involved in the Manhattan Project, was the one who discovered that plutonium was the element necessary to produce a spontaneous fission reaction. His contributions to the Manhattan Project were not included in the film as much as they were recognized in real-life. In the film, a scene depicts the May 31, 1945, meeting of the Interim Committee, which J. Robert Oppenheimer attended as a member of
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{
"page_id": 66850554,
"source": null,
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the Scientific Panel of consultants. In this scene, Secretary of War Henry L. Stimson is portrayed ordering the removal of Kyoto from the list of top atomic bomb targets, allegedly because it was a favored honeymoon destination for him and his wife. However, historian of science and nuclear weapons, Alex Wellerstein, clarifies that this portrayal is a myth. According to Wellerstein, Stimson's diary from his 1926 travels with his wife does not mention Kyoto, and the only brief visit they made there was in 1929, during a single night stay while on a "fact-finding" mission related to his role as Governor-General of the Philippines. The film's depiction overlooks that Stimson's objection to targeting Kyoto was primarily strategic rather than personal. He expressed this viewpoint to President Truman on multiple occasions, including at the Potsdam Conference. Stimson wrote in his diary on July 24, 1945, "He [Truman] again reiterated with the utmost emphasis his own concurring belief on that subject, and he was particularly emphatic in agreeing with my suggestion that if elimination was not done, the bitterness which would be caused by such a wanton act might make it impossible during the long post-war period to reconcile the Japanese to us in that area rather than to the Russians." == Accolades == Oppenheimer earned a leading 13 nominations at the 96th Academy Awards, becoming Nolan's most Oscar-nominated film. At the ceremony, the film won Best Picture, Best Director, Best Actor for Murphy, Best Supporting Actor for Downey Jr., Best Cinematography, Best Film Editing, and Best Original Score. Besides composer Göransson, all recipients were first-time Oscar winners, including Nolan, Thomas, Roven, Downey Jr. and van Hoytema, who had each earned previous Academy Award nominations. Oppenheimer became both the highest-grossing and longest Best Picture winning film since 2003's The Lord of the
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{
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"source": null,
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Rings: The Return of the King. The film was also nominated for Best Supporting Actress for Blunt, Best Adapted Screenplay, Best Costume Design, Best Makeup and Hairstyling, Best Production Design, and Best Sound. The film won numerous other accolades. It won a leading five Golden Globe Awards, receiving Best Motion Picture – Drama, Best Director for Nolan, Best Actor in a Motion Picture – Drama for Murphy, Best Supporting Actor – Motion Picture for Downey Jr., and Best Original Score for Göransson at the 81st ceremony. The National Board of Review and the American Film Institute named Oppenheimer one of the top-ten films of 2023. Oppenheimer received nominations for 13 Critics' Choice Movie Awards (winning eight), 13 British Academy Film Awards (winning seven), 14 Saturn Awards (winning four), and four Screen Actors Guild Awards (winning three), while its score earned three nominations at the 66th Annual Grammy Awards (winning one). == See also == List of films about nuclear issues List of World War II films since 1990 Oppenheimer, a 1980 TV series about Oppenheimer, starring Sam Waterston in the title role Fat Man and Little Boy, 1989 film about the Manhattan Project, starring Paul Newman as General Groves and Dwight Schultz as Oppenheimer Day One, 1989 TV film about the Manhattan Project, starring Brian Dennehy as General Groves and David Strathairn as Oppenheimer Doctor Atomic, a 2005 opera about Oppenheimer, composed by John Adams == Notes == == References == == Further reading == Johnson-Roehr, S. N. (March 7, 2024). "The Annotated Oppenheimer". JSTOR Daily. Retrieved March 8, 2024. Bird, Kai (July 17, 2023). "The Tragedy of J. Robert Oppenheimer". New York Times. Retrieved November 5, 2024. == External links == Official website Oppenheimer at IMDb
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