CSE , Midterm 3. Fall The exam will include all the lectures, class discussions, homework s and piazza posts up to the exam date. Joe Blitzstein. See Piazza for Zoom Links. Mutsumi Nakamura. Jerry Cain Gates Spring Patt and Sanjay J.
The function copyandsub reads from one array and writes to the other. CSE Lab 3 For this Lab, you will have to write a java program that asks the user to enter grades for homework, midterm exam, and final exam. Lab Sessions.
Tech and for others also college students. Be sure to list a constant of appropriate type e. Next, the program prompts for data about midterm 2 and then about Spring , Mon, Wed, Fri: pm - pm in Gates B CSc Sample Midterm Exam 1 1. Will be held during lecture see schedule. Does anyone have any tips or resources they'd be willing share with me? I'd really appreciate any help you can give. Empty White Paper. More recently, Gonzalez-Rincon et al.
Overall, they observed that pre-transformed FLs samples were more mutated and presented greater subclonal heterogeneity than non-transformed forms. With this information, the authors conclude, it could be easier to identify patients at higher risk of transformation [59].
With the purpose of investigating the pathogenic causes of chemoresistance and relapse in DLBCL, a work sequenced VDJ junctions in 14 pairs of matched diagnosis—relapse tumours [60]. The results of this study proposed two mechanisms of clonal evolution in which the early-divergent mode found two distinct clones, the diagnostic one and the relapsing one, that diverged early; and the late-divergent mode, in which relapse clones descended directly from diagnostic clones with minor divergence.
Indeed, they identified in epigenetic modifiers such as KMT2D the potential early driving mutation targets, and in immune escape alterations the relapse-associated events [60]. In the former, Fornecher et al.
In the latter research, Rushton et al. Collectively, they found that DLBCL patients with such mutations present a higher risk of treatment failure [64]. Furthermore, they analysed the benefits of the addition of bortezomib to standard R-CHOP therapy; the collected data suggested a possible positive response to bortezomib [77]. In another work, Ennishi et al. So, it is well known that there are diverse MYC alteration mechanisms, and other new ones are being discovered. For example, very recently Gallardo et al.
Furthermore, hnRNP K overexpression in transgenic mice induced the development of lymphomas and reduced survival. Indeed, through global screening experiments and biochemical assays, they showed that hnRNP K is capable of post-transcriptionally and translationally regulating MYC.
In their report, Scott et al. In an interesting study conducted by Chong et al. They characterized the partner gene in 88 cases and identified a breakpoint cluster region upstream of the MYC coding region and in intron 1. More recently, another work confirmed these data: by analyzing a large cohort of DLBCL patients, Rosenwald et al.
As regards DH lymphomas, MYC and BCL2 rearrangements frequently trigger the corresponding protein overexpression, characterizing a specific group called DPE lymphomas [90,91], clinically featuring rapid progression and poor outcome.
Recently, a study by Uchida et al. In vitro studies on DH and DPE lymphoma-derived cell lines revealed that the survival of neoplastic cells seems to depend on BCL2 activity rather than that of MCL1, a protein with a pro-survival function.
In primary lymphoma cell cultures, venetoclax was able to induce apoptosis even at low doses [92], showing venetoclax as a promising strategy for the treatment of DH-DPE lymphomas. However, further investigations are needed before coming to definitive conclusions.
Indeed, it reflects the real tumour genomic heterogeneity, as demonstrated by the observation of varies mutations maybe originating from different tumour-associated localizations. Further, through liquid biopsy the response to therapy and minimal residual disease can be monitored, as well as transformation or chemoresistance emerging by tracking genetic evolution through ctDNA analysis over time [94,96].
A work conducted liquid biopsy through targeted-NGS on a set of lymphoma- and cancer-relevant genes in 50 lymphoma patients in order to establish the mutation profiles of different lymphoma subtypes and evaluate the correlation between the cfDNA concentration and other clinical indexes such as serum LDH and IPI [].
CIRI for monitoring DLBCL patients considers a total of six risk factors, including the IPI, COO, interim imaging iPET , along with ctDNA measurements prior to cycles one, two, and three of therapy, and has been demonstrated to improve outcome prediction compared to conventional risk models, thus enabling therapy selection in the perspective of personalized medicine []. Moreover, a problem of the first line studies is that in relapsed setting drugs have a short duration of responses and no plateau.
Indeed, the efficacy of some drugs could be reduced because of incorrect combination with chemotherapeutic agents or insufficient dosage, as well as because of tumour-specific peculiarities []. However, despite the enormous excitement about the hypothesis of using targeted agents for patient personalized treatment, there are a series of inherent difficulties to be surmounted.
Randomized trials on the addition of targeted drugs ibrutinib, everolimus, bortezomib, and lenalidomide to standard chemotherapy did not demonstrate a clear advantage [—], and in some circumstances the use of targeted agents alone has been hypothesized. In other cases, the opportunity of drug combinations has been discussed [], as a better response can be obtained than with each drug alone.
Indeed, although nowadays a number of new potent drugs are available, it is equally true that there could be a wide list of drug combinations that could be employed for patient treatment.
The opportunity of using drug combinations that attack important cancer-signalling pathways at the same time from multiple fronts raises the chance of therapeutic success, especially in the treatment of tumours such as DLBCL that present with complex genetic heterogeneity. Indeed, this approach can reduce treatment resistance, which can frequently be due to pathway redundancies, cancer cell heterogeneity, and disease evolution [,]. A clear example that confirms this concept is R-CHOP, which has recently been demonstrated to be effective and curative thanks to low cross-resistance, rather than synergy among drugs [].
Cancers , 12 12 of 20 DeepSynergy, to elaborate drug combinations integrating the data deriving from gene expression Cancers , 12, 12 of 20 analysis of 39 cancer cell lines with the chemical peculiarities of 38 anti-cancer drugs []. However, some authors observed that this method uses large numbers of known synergistic drug combinations, frequently not However, providing today aonly a narrow list hypothesis of of theapproved potentialdrug combinations mechanism ofisaavailable; specificindeed, they drug combination mostly derive from empirical clinical experience rather than rational design.
To meet this need, synergy. Other approaches were then developed in order to identify the underlying molecular some computational models have been developed that integrate the tumour genomic signatures with mechanisms of disease; pharmacological one example profiles of drugs. In is , Combinatorial Drug Assembler Preuer et al. However, Another model is some authors observed that this method uses large numbers of TIMMA [], which identifies drugs targeting multiple driver pathways by elaborating and known synergistic drug combinations, frequently not providing a hypothesis of the potential mechanism of a specific drug combination combining drug screening data and drug target interactions into a target inhibition network synergy.
Other approaches were then developed in order to identify the underlying molecular framework. However, mechanisms the one of disease; survival example pathways to beDrug is Combinatorial targeted Assembler were identified CDA based on empirical [], a pathway-based selection,model not considering genomic elaborated to discover drugdata. Anothersystem model isbiology TIMMAtool [],that they called which identifies drugs targeting multiple driver pathways by elaborating and DrugComboExplorer, which combines specific genomic characteristics of cancer types i.
However, the survival pathways, interactome and pharmacological data with pharmacogenomic profiles of drugs and pathways to be targeted were identified based on empirical selection, not considering genomic data. Indeed, which DrugComboExplorer, by adopting combines aspecific data-driven genomic strategy characteristicsandofby combining cancer types i. Indeed, by adopting a data-driven strategy and by combining multi-omics data DNA and is able to perform large-scale drug combination prediction 15,, available drug seq, gene copy number, DNA methylation, and RNA-seq data of individual cancer patients, this tool combinations.
Surely, this kind of approach is still in its infancy as the authors admit, but further investigations Surely, this kind of approach is still in its infancy as the authors admit, but further investigations are ongoing to try to are ongoing to apply these try to apply models these models totospecific cancercases specific cancer cases in clinical in clinical practice practice in orderintoorder to identify identify personalized drug drug personalized combinations combinationsand moreefficient and more efficient treatment treatment plans forplans for individual individual patients [].
Then, large large scale collaborations scale collaborations shouldshould be scheduled be scheduled integratingintegrating mulit-omics data, mulit-omics Bayesian trialdata, design,Bayesian and trial early shared endpoints based on, for example, CIRI or any interim guided design, and early shared endpoints based on, for example, CIRI or any interim guided models to test models to test in vivo the reliability of these drug combination-predicting models Figure 1.
Figure 1. Through their integration Figure 1. From the perspective of personalized biologic features. This information will be then combined with drug-specific peculiarities to generate a medicine,listthe treatment of targeted drug option will for combinations be the stitched onto choice of thetherapy the best patientforafter a multi-omic analysis of the each patient.
This information will be then combined with drug-specific peculiarities to generate a list of targeted drug combinations for the choice of the best therapy for each patient. Conclusions The attentive observer has surely realized that there is currently a dichotomy between the potentialities deriving from the recent discoveries for DLBCL diagnosis, prognosis, and treatment, and patient management in real clinical life.
Probably, today we are still far from this goal, as standardizations and clinical trial designs are still needed to render molecularly driven approaches really achievable. In any case, the bases are there, allowing us to pursue the goal of realizing targeted therapy for DLBCL.
Conflicts of Interest: The authors declare no conflict of interest. References 1. Swerdlow, S. The revision of the World Health Organization classification of lymphoid neoplasms. Blood , , — Poeschel, V. Blood , , Sehn, L. Introduction of combined CHOP plus rituximab therapy dramatically improved outcome of diffuse large B-cell lymphoma in British Columbia.
Philip, T. Van Imhoff, G. Crump, M. Van Den Neste, E. Outcome of patients with relapsed diffuse large B-cell lymphoma who fail second-line salvage regimens in the International CORAL study. Bone Marrow Transplant. Jackson, H. Driving CAR T-cells forward. Chow, V. Bachanova, V. Modern management of relapsed and refractory aggressive B-cell lymphoma: A perspective on the current treatment landscape and patient selection for CAR T-cell therapy.
Blood Rev. Neelapu, S. Shipp, M. Zhou, Z. Alizadeh, A. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature , , — Fisher, R. Next, the program prompts for data about midterm 2 and then about Spring , Mon, Wed, Fri: pm - pm in Gates B CSE midterm and final exams must be taken at standard assigned times. Other sets by this creator.
Expression Value Midterm exam. Only RUB CSE , Midterm 3. Mutsumi Nakamura. Stat Midterm Solutions, Fall Cse - lab 4. Web Link: garygraphics-2c2d1. The Course Website. Manqing Zhang. Quickly memorize the terms, phrases and much more.
Blogs and study guide for Stony Brook University Midterms. Please see the Assignments page for more details. After midterm the course teacher also give the solution of the midterm. This is a manual update an advisor needs to make. Other designs and some different answers were also acceptable. Recitation 5. Does anyone have any tips or resources they'd be willing share with me?
I'd really appreciate any help you can give. Log in with Facebook Log in with Google. Remember me on this computer. Enter the email address you signed up with and we'll email you a reset link. Need an account? Click here to sign up. Download Free PDF. A short summary of this paper. Download Download PDF.
Translate PDF. Department of Defense. Today, millions of hosts connect to this network, which now is known as the Internet. A host, more commonly known today as a server, is any computer that provides services and connections to other computers on a network. The mission of the W3C is to ensure the continued growth of the web.
A dongle is a small device that connects to a computer. Broadband Internet service is known for its fast data transfer speeds and its always-on connection. Wireless options include: Wi- Fi, mobile broadband, fixed wireless, and satellite Internet service.
A hot spot is a wireless network that provides Internet connections to mobile computers and devices. May not be scanned, copied or duplicated, or posted to a publicly accessible website, in whole or in part. ISP stands for Internet service provider. Computers and devices connected to the Internet work together to transfer data around the world using servers and clients and various wired and wireless transmission media. On the Internet, your computer or device is a client that can access data and services on a variety of servers.
Several main transmission media carry the heaviest amount of traffic, or communications activity, on the Internet. These major carriers of network traffic are known collectively as the Internet backbone. An IP address is a sequence of numbers that uniquely identifies the location of each computer or device connected to the Internet. Due to the growth of the Internet, the original IPv4 addresses began dwindling in availability.
The IPv6 scheme increased the available number of IP addresses exponentially. A domain name is a text-based name that corresponds to the IP address of a server that hosts a website.
Some generic TLDs and their purposes include:. Cybersquatters purchase unused or lapsed domain names so that they can profit from selling them. Cybersquatters sometimes will sell you the domain name, but some take advantage of people trying to reach a more popular website to promote their own business or needs.
Cybersquatters look for out-of-date registrations and buy them so that the original website owner must buy them back. Cybersquatters often purchase domain names with common words, alternate spellings of trademarked terms, or celebrity names.
When you enter a domain name in a browser, a DNS server translates the domain name to its associated IP address so that the request can be routed to the correct computer. Visitors to a static webpage all see the same content each time they view the webpage. With a dynamic webpage, by contrast, the content of the webpage generates each time a user displays it.
The web consists of a worldwide collection of electronic documents. Each electronic document on the web is called a webpage, which can contain text, graphics, animation, audio, and video. A website is a collection of related webpages and associated items, such as documents and photos, stored on a web server. A web server is a computer that delivers requested webpages to your computer or mobile device. A browser is an application that enables users with an Internet connection to access and view webpages on a computer or mobile device.
Current browsers typically support tabbed browsing, where the top of the browser shows a tab similar to a file folder tab for each webpage you display. Follow these guidelines when browsing: verify the website is safe; turn off location sharing; clear your browsing history; never store passwords; use a phishing filter; enable a pop- up blocker; use private browsing; and use a proxy server.
A web feed contains content that has changed on a website. A web app is an application stored on a web server that you access through a browser.
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