GLSI stock: Up 1,600% In 2 Days, Is It Too Late To Buy This Hot Biotech Stock?

 April 6, 2021

Here is the article. 

Yesterday, shares of small-cap biotech Greenwich LifeSciences (NASDAQ:GLSI) surged by nearly 3,000% to an all-time high of $158.07. Today, shares are priced at $90.57, representing stock price growth of 1,650% in two days. The wild trading followed the announcement of positive clinical results for its sole immunotherapy candidate, GP2. Immunotherapies treat cancer by boosting the body's own immune system to fight it.

Are investors buying into irrational exuberance? Or did Greenwich find an effective treatment that can stop the recurrence of breast cancer? Let's find out.

What's the hype all about?

The enthusiasm surrounding Greenwich stock seems to originate from a subgroup of patients who had 0% recurrence of their breast cancer within five years after treatment with GP2. In this placebo-controlled phase 2b clinical trial involving 168 people, breast cancer patients first underwent surgery for tumor removal.

Afterward, treatment to prevent the cancer's reappearance began. Some participants received treatment with trastuzumab, an approved immunotherapy, while some did not. Regardless of whether a study participant took trastuzumab, trial investigators randomized them into one of two cohorts, one with GP2 plus GM-CSF and the other with a placebo plus GM-CSF; GM-CSF is an approved immunoadjuvant that stimulates the performance of immune cells. Out of the four groups, the patients who received trastuzumab and then GP2 plus GM-CSF had no relapses of breast cancer.

Is the data really this good?

Unfortunately, there are more significant limitations to the study than meet the eye.

First of all, the placebo cohort also had a fantastic performance. In fact, only 10.6% of women in this subgroup saw a recurrence of their breast cancer within the same time frame. Compared to the GP2 cohort, the difference was statistically significant but not robust. For example, in trastuzumab's pivotal study, the drug demonstrated considerable efficacy in treating breast cancer.

More critically, among the two groups of patients who did not take trastuzumab, 22.4% of patients in the GP2 cohort saw their breast cancer relapse after five years, compared to 22.1% in the placebo cohort. In other words, the experimental therapy failed to prevent the recurrence of breast cancer in this instance.

Lastly, there are no results yet on whether cancer will return beyond a period of five years for patients in the GP2 cohort who were first treated with trastuzumab. However, the money, time, and effort required to investigate cancer drugs in decade-long trials is a problem that affects the entire oncological treatment industry. It's by no means specific to Greenwich LifeSciences.

Is the stock a buy or sell?

The main takeaway of the phase 2 study is that GP2 is somewhat effective at preventing the reappearance of breast cancer when given in conjunction with trastuzumab, but does not work on its own. However, the therapeutic still requires validation in a large-scale phase 3 study, which could take a few more years. So Greenwich LifeSciences would be a speculative buy, or perhaps a tiny investment for a biotech investor with a tolerance for risk.

That said, Greenwich certainly deserves credit for being able to advance an immunotherapy candidate to this stage while spending $27.9 million in research and operating costs since inception. Right now, the company has little cash and no revenue, so it would probably need to raise equity on these results to fund GP2's late-stage clinical trial.

If that succeeds down the line, then Greenwich shares could be up for a huge pop. The company only has a market cap of $1 billion as of Dec. 10. However, big pharma companies frequently acquire clinical-stage biotech companies with experimental cancer therapies in deals worth as much as $5 billion to $10 billion.

Since GP2 has a therapeutic signal compared to placebo at this stage, and the company is still a small cap, investors should consider opening a small stake if they find Greenwich intriguing. For those who don't like the volatility, are doubtful of the results, or want to wait for a better price down the road, check out these alternative biotech stocks instead.

Motley Fool’s 5G Stock Pick

For the first time ever, Apple will release an iPhone that is 5G ready and 5G will supercharge this new iPhone.

That’s why Apple analysts are convinced that an unprecedented number of Apple fans will sprint to upgrade to this new iPhone.

But before you run out and buy shares of Apple, there’s something you need to know, because there might be an even more lucrative way to play the coming iPhone boom.

Legendary Canadian stock analyst Iain Butler and his team at Stock Advisor Canada have identified a tiny American company (52 times smaller than Apple’s) that seems perfectly positioned for the coming iPhone supercycle.

That’s why so many investors are buzzing with excitement about the new report from Iain Butler’s team at Stock Advisor Canada. The name of this report is “iPhone Super-Cycle: An Investor’s Guide to the Coming Apple Tsunami.”

This new report reveals the reasons why we think every forward-thinking investor should be paying close attention to this revolutionary new industry.

My homework

GTE stock research: Colombia Is Preparing For A Fracking Boom

 April 6, 2021

Here is the article. 

I like to highlight something new to me. I invested over 10,000 shares of GTE.TO. 

Editor OilPrice.com

March 29, 2021·6 min read

It was roughly a decade ago when hydraulic fracturing, known as fracking, was identified as a crucial means for boosting Colombia’s meager hydrocarbon reserves and production. A shortage of proved crude oil and natural gas reserves along with declining production is threatening Colombia’s economy. Despite only possessing two billion barrels of proved oil reserves with a short six-year production life, Colombia is highly reliant upon petroleum production to drive the economy. During 2020, at the height of the pandemic and oil price crash, petroleum accounted for 28% of exports by income, 3% of gross domestic product, and 17% of fiscal revenue. A dearth of significant conventional oil discoveries since the late 1990s means Colombia must find alternate means of boosting crude oil and natural gas reserves if its hydrocarbon-dependent economy is to grow. In fact, a lack of significant discoveries combined with weak natural gas production due to rising decline rates at aging offshore fields and growing demand forced Bogota to start importing liquified natural gas in 2017. This shortage triggered a crisis that challenged the Andean country’s energy security, forcing the national government to work feverishly to resolve the crisis by implementing incentives aimed at promoting exploration and development activity, including paying higher than market natural gas prices at the wellhead.

In 2018, when President Ivan Duque was championing fracking as means of addressing Colombia’s lack of hydrocarbon reserves, the Council of State, the country’s highest administrative tribunal, placed a moratorium on the controversial technique. That essentially prevented the introduction of fracking in Colombia as a means of extracting crude oil and natural gas. In 2019 the tribunal upheld the ban on fracking but roughly a week after announcing that decision clarified it did not include pilot projects. A 2020 bid to block fracking pilots failed and in September that year the National Hydrocarbon Agency (ANH – Spanish initials) finalized the regulations for selecting pilot participants. Colombia’s fracking pilots are restricted to be conducted in the Middle Magdalena Valley and Cesar-Ranchería Basins. The head of the ANH, Armando Zamora, in a March 2021 Reuters article, stated he expects the 2018 moratorium on fracking in Colombia to be lifted during 2022 when environmental regulations are modified.

The Middle Magdalena Valley Basin, located in central Colombia between the eastern and central Andes mountain ranges, has over 40 discovered conventional oilfields with the U.S. Geological Service (USGS) predicting it holds undiscovered oil resources of up to 1.4 billion barrels.

EIA

Source: U.S. EIA.

Since 1918, when crude oil was first discovered in Colombia at the La Cira-Infantas oilfield in the basin, it has produced most of Colombia’s oil. The key fracking target in the Middle Magdalena Valley Basin is the La Luna geological formation which has been compared to the prolific U.S. Eagle Ford shale play. It is a Cretaceous age geological formation typified as a classic shale-gas system in which the rock is the source, reservoir, and seal. The USGS estimated in 2017 that the La Luna possesses undiscovered shale oil resources of up to 521 million barrels and over two trillion cubic feet of natural gas. It has been predicted that the Middle Magdalena Valley basin, in total, contains unconventional crude oil resources of up to seven billion barrels, or more than triple Colombia’s current proved reserves and 13 trillion cubic feet of natural gas. Those copious hydrocarbon resources, if proven to be commercially viable to extract, will resolve the significant economic downside posed by Colombia’s limited crude oil and natural gas reserves.

The push to bring fracking pilots online is gaining considerable momentum after a fraught 2020 where significant risks, including sharply weaker oil prices and continued community opposition, indicated they may never eventuate. National oil company Ecopetrol, which is 88.49% owned by the Colombian government, launched the Kale fracking pilot in the Middle Magdalena Valley in the department of Santander near the town of Puerto Wilches. The national oil company has budgeted almost $77 million to develop the project, with drilling scheduled to commence during the second half of 2021. Earlier this month global oil supermajor ExxonMobil also announced it had submitted a proposal for a fracking project in the Middle Magdalena Valley near Puerto Wilches. Exxon has earmarked $57 million for the project, which has yet to be approved by the ANH.

Related: Houthi Rebels Launch Missile Attack On Saudi Oil Terminal

The economic importance of developing fracking in Colombia cannot be emphasized enough. The Andean country’s peak petroleum industry body, the Colombian Petroleum Association (ACP – Spanish initials), believes commercial fracking in the Andean country could eventually add 450,000 barrels of daily production to current production and attract $5 billion of investment. That will provide an important source of revenue for a cash-strapped national government still reeling from the pandemic’s severe economic fallout and crude oil’s prolonged price slump. Bogota is struggling to restart a stalled economy which, despite being projected to grow by 4% during 2021 compared to contracting by 7.8% in 2020, will see the budget deficit blowout by almost one percent year over year to 8.6% of GDP. Unemployment is still alarmingly high with DANE, the national statistical agency, reporting it reached 17.3% in January 2021 the highest since July 2020 at the peak of Colombia’s pandemic lockdown. Those worrying numbers indicate that Colombia is still unable to shake off the profound economic aftermath of the pandemic, indicating that Bogota needs to find ways to restart the economy.

The Andean country’s considerable economic dependence on hydrocarbon extraction makes it especially vulnerable to its limited oil and natural gas reserves, including their short production life and oil price slumps. It appears that Colombia is unable to end its addiction to extracting fossil fuels to power the economy. The Andean country’s energy minister recently stated Colombia would double down on thermal coal mining, despite it being the first fossil fuel to be phased out as part of the fight against global warming. By bolstering hydrocarbon reserves and production Bogota will only further expose the economy to volatile oil prices and the immense downside which exists once peak oil demand arises, which according to some industry analysts could be in as little as seven years. Considerable community opposition to fracking remains tremendous. That, combined with the petroleum industry’s slowly waning social license and ongoing security issues, is creating considerable uncertainty which is weighing on investment in unconventional oil and gas production in Colombia.

7.1 Incrementally Refactoring a Monolith Into Microservices Event Driven Microservices

 April 5, 2021

Here is the link. 

I will take some notes and then figure out what to learn next. 

Interview: Chris Richardson Of Microservices.io

 April 5, 2021

Here is the link. 

Chris Richardson, creator of Microsrevices.io, talks about distributed data in microservices, common pitfalls for developers and architects to avoid, and the process of moving away from the monolith.

6.7 Event Sourcing and Microservices Event Driven Microservices

April 5, 2021

Here is the link. 

Aggregates + Event sourcing = Modular domain model 

Modular domain model

tightly coupled ACID 

Event sourcing 

Microservice architecture 

6.6 Implementing Queries in an Event Source Application Event Driven Microservices

 April 5, 2021

Here is the link. 

Persisting a customer and order history in MongoDB

Denormalized = efficient lookup 

Other kinds of views

AWS cloud search

• Text search as a service
• View updater batches aggregate to index
• View query service does text search

AWS DynamoDB

• NoSQL as a Service
• On demand scalable specify desired read/write capacity
• Document and key value data models
• Useful for denormalized UI oriented views

Benefits and drawbacks of CQRS

Benefits

• Necessary in an event sourced architecture
• Separation of concerns = simpler command and query models
• Supports multiple denormalized views
• Improved scalability and performance

Drawbacks

• Complexity
• Potential code duplication
• Replication lag/eventually consistent views

Domain-driven design | Book reading: Design domain-driven design Eric Evens

 April 5, 2021

Domain-driven design (DDD) is the concept that the structure and language of software code (class names, class methods, class variables) should match the business domain. For example, if a software processes loan applications, it might have classes such as LoanApplication and Customer, and methods such as AcceptOffer and Withdraw.

DDD connects the implementation to an evolving model.^[1]

Domain-driven design is predicated on the following goals:

• placing the project's primary focus on the core domain and domain logic;
• basing complex designs on a model of the domain;
• initiating a creative collaboration between technical and domain experts to iteratively refine a conceptual model that addresses particular domain problems.

The term was coined by Eric Evans in his book of the same title.

Relationship to other ideas[edit]

Object-oriented analysis and design

Although, in theory, the general idea of DDD need not be restricted to object-oriented approaches, in practice, DDD seeks to exploit the advantages that object-oriented techniques make possible. These include entities/aggregate roots as receivers of commands/method invocations and the encapsulation of state within foremost aggregate roots and on a higher architectural level, bounded contexts.

Model-driven engineering (MDE) and Model-driven architecture (MDA)

While DDD is compatible with MDA/MDE (where MDE can be regarded as a superset of MDA) the intent of the two concepts is somewhat different. MDA is concerned more with the means of translating a model into code for different technology platforms than with the practice of defining better domain models. The techniques provided by MDE (to model domains, to create DSLs to facilitate the communication between domain experts and developers,...) facilitate the application of DDD in practice and help DDD practitioners to get more out of their models. Thanks to the model transformation and code generation techniques of MDE, the domain model can be used not only to represent the domain but also to generate the actual software system that will be used to manage it. This picture shows a possible representation of DDD and MDE combined.

Plain Old Java Objects (POJOs) and Plain Old CLR Objects (POCOs)

POJOs and POCOs are technical implementation concepts, specific to Java and the .NET Framework respectively. However, the emergence of the terms POJO and POCO reflect a growing view that, within the context of either of those technical platforms, domain objects should be defined purely to implement the business behaviour of the corresponding domain concept, rather than be defined by the requirements of a more specific technology framework.

The naked objects pattern

Based on the premise that if you have a good enough domain model, the user interface can simply be a reflection of this domain model; and that if you require the user interface to be a direct reflection of the domain model, then this will force the design of a better domain model.^[4]

Domain-specific modeling (DSM)

DSM is DDD applied through the use of Domain-specific languages.

Domain-specific language (DSL)

DDD does not specifically require the use of a DSL, though it could be used to help define a DSL and support methods like domain-specific multimodeling.

Aspect-oriented programming (AOP)

AOP makes it easy to factor out technical concerns (such as security, transaction management, logging) from a domain model, and as such makes it easier to design and implement domain models that focus purely on the business logic.

Command Query Responsibility Segregation (CQRS)

CQRS is an architectural pattern for separation of reads from writes, where the former is a Query and the latter is a Command. Commands mutate state and are hence approximately equivalent to method invocation on aggregate roots/entities. Queries read state but do not mutate it. CQRS is a derivative architectural pattern from the design pattern called Command and Query Separation (CQS) which was coined by Bertrand Meyer. While CQRS does not require DDD, domain-driven design makes the distinction between commands and queries explicit, around the concept of an aggregate root. The idea is that a given aggregate root has a method that corresponds to a command and a command handler invokes the method on the aggregate root. The aggregate root is responsible for performing the logic of the operation and yielding either a number of events or a failure (exception or execution result enumeration/number) response OR (if Event Sourcing (ES) is not used) just mutating its state for a persister implementation such as an ORM to write to a data store, while the command handler is responsible for pulling in infrastructure concerns related to the saving of the aggregate root's state or events and creating the needed contexts (e.g., transactions).

Event Sourcing (ES)

An architectural pattern which warrants that your entities (as per Eric Evans' definition) do not track their internal state by means of direct serialization or O/R mapping, but by means of reading and committing events to an event store. Where ES is combined with CQRS and DDD, aggregate roots are responsible for thoroughly validating and applying commands (often by means of having their instance methods invoked from a Command Handler), and then publishing a single or a set of events which is also the foundation upon which the aggregate roots base their logic for dealing with method invocations. Hence, the input is a command and the output is one or many events which are transactionally (single commit) saved to an event store, and then often published on a message broker for the benefit of those interested (often the views are interested; they are then queried using Query-messages). When modeling your aggregate roots to output events, you can isolate the internal state even further than would be possible when projecting read-data from your entities, as is done in standard n-tier data-passing architectures. One significant benefit from this is that tooling such as axiomatic theorem provers (e.g., Microsoft Contracts and CHESS^[5]) are easier to apply, as the aggregate root comprehensively hides its internal state. Events are often persisted based on the version of the aggregate root instance, which yields a domain model that synchronizes in distributed systems around the concept of optimistic concurrency.

Vancouver IT companies

 如果你决定留在温哥华, 那么求稳去知名上市公司的. 本地office有些工作经验的可以尝试, remote然而个人认为兼顾成长收入和稳定的选择应该是加入美国中后期startup公司在温哥华的office或者remote

上市公司就不多说了, Amazon主要是招的人多, Microsoft第二, Apple, Facebook, Google, Oracle招的人是真少, 其他的不错的有 Salesforce, Tableau, Square, Slack, Splunk, Segment(Twilio), Asana, Shopify, Workday, Mastercard, 基本错不了, Cisco和SAP福利不错Fortinet, GEdigital, Broadcom, Move(Realtorcom), Arista据说还可以

如果可以接受remote, 那选择是相当之多. 包括Twitter, coursera, Wish, Intuit, SurveyMonkey, MongoDB等. 

Startup

在温哥华开office有很多无法一一列举处于中后期的有Dialpad, Chime, Postmates

其他startup中比较有名的有Flipboard, Mozilla, Kickstarter, Zenefits已被收购单论工资还不错

除此之外温哥华本地也有很多Startup, 像Slack, 原本就是温哥华发家的. 

本地startup中做的比较好的有Hootsuite, Visier, Clio, Trulioo, Axiom, Zen(CryptoKitty/NFT), Tasktop, D-Wave(QuantumComputer), 饭团, POF等.

如果可以接受remote那么其实优秀的startup相当之多Esty, Stripe, Instacart, Brex, Okta, Coinbase, Zapier, Gusto, PagerDuty等

温哥华游戏公司也挺多, 不过总的来说性价比不高. 钱不多事不少, 大一些的有EA, Demonware(ActivisionBlizzard), Relic, Skybox, IUGO, Kabam, TheCoalition(GearsofWar)

小的就更多了, Archiact, A ThinkingApe, Klei, EastSideGames

数不过来其实Capcom, Nintendo, Bandai, Namco, KOEI.

在温哥华都有办公室但是招人非常少-baidu, 1point3acres

温哥华还有一些公司不完全符合上述条件但是机会也不错比如FinTech方面有RBC的lab, Borealis AI高频交易公司, DRW应该都是不差钱的. 

至于Shaw, Telus, Bell之类的就不太熟悉了.

总的来说温哥华的收入和美国相比要低不少. 

这是事实, 然而因为温哥华和硅谷处于同一时区, 所以这样的势能差逐渐被很多公司发现并利用. 

加上政府的优惠税收政策和宽松的移民政策使得这几年到温哥华来开office的公司越来越多. 

此外疫情也是一个相当重要的因素, 很多公司意识到了remote是完全可行的. 所以remote的机会也越来越多.

以上这些因素导致了温哥华码农这几年的待遇逐步提高并且长期趋势看好. 当然无论如何南边的机会肯定更多是没错的